Proposal to add new mode of inheritance to classification form

[sksmi]

"semidominant"

e.g. https://search.clinicalgenome.org/kb/gene-validity/dd6376b1-1593-461f-bfc8-cec5cfb1c3f8--2020-02-26T17:00:00

[EmmaTudini]

Agree - think we should align to clingen more closely.

Options are

• Autosomal dominant inheritance- adjectives include with maternal imprinting, with paternal imprinting, sex-limited, with genetic anticipation, primarily or exclusively de novo, mosaic
• Autosomal recessive inheritance- with genetic anticipation, sex-limited
• Semidominant inheritance
• Mitochondrial inheritance- primarily or exclusively homoplasmic, primarily or exclusively heteroplasmic
• X-linked inheritance- dominant, recessive, primarily recessive with milder female expression
• Other - which includes Y-linked inheritance, somatic mutation, multifactorial inheritance, co-dominant inheritance and mosaic
• Undetermined mode of inheritance

We currently have autosomal_dominant : Autosomal dominant autosomal_recessive : Autosomal recessive autosomal_unknown : Autosomal unknown sex_limited_autosomal_dominant : Sex limited autosomal dominant x_linked : X-linked x_linked_recessive : X-linked recessive x_linked_dominant : X-linked dominant y_linked : Y-linked mitochondrial : Mitochondrial oligogenic : Oligogenic somatic : Somatic unknown : Unknown other : Other digenic_recessive : Digenic recessive digenic_dominant : Digenic dominant isolated_cases : Isolated cases multifactorial : Multifactorial imprinting : Imprinting

Will likely need to leave imprinting as it's own value as one lab providing this info does not specify the type of imprinting. Including adjectives will likely be useful in the long run, but doubt we'll receive that level of info from shariant users. For "other" would just add values included in other.

[EmmaTudini]

Clinvar accepted values at the moment

"Autosomal dominant inheritance", "Autosomal recessive inheritance", "Mitochondrial inheritance", "Somatic mutation", "Genetic anticipation", "Sporadic", "Sex-limited autosomal dominant", "X-linked recessive inheritance", "X-linked dominant inheritance", "Y-linked inheritance", "Other", "X-linked inheritance", "Codominant", "Semidominant inheritance", "Autosomal unknown", "Autosomal dominant inheritance with maternal imprinting", "Autosomal dominant inheritance with paternal imprinting", "Multifactorial inheritance", "Unknown mechanism", "Oligogenic inheritance"

[TheMadBug]

This SQL will update environments to have the extra option

UPDATE "public"."classification_evidencekey"
SET options=E'[{"key": "autosomal_dominant", "index": 1, "label": "", "clinvar": "Autosomal dominant inheritance"}, {"key": "autosomal_recessive", "index": 2, "label": "", "clinvar": "Autosomal recessive inheritance"}, {"key": "autosomal_unknown", "index": 3, "label": "", "clinvar": "Autosomal unknown"}, {"key": "sex_limited_autosomal_dominant", "index": 4, "label": "", "clinvar": "Sex-limited autosomal dominant"}, {"key": "semidominant_inheritance", "index": 19, "label": "", "clinvar": "Semidominant inheritance"}, {"key": "x_linked", "index": 5, "label": "", "clinvar": "X-linked inheritance"}, {"key": "x_linked_recessive", "index": 6, "label": "", "clinvar": "X-linked recessive inheritance"}, {"key": "x_linked_dominant", "index": 7, "label": "", "clinvar": "X-linked dominant inheritance"}, {"key": "y_linked", "index": 8, "label": "", "clinvar": "Y-linked inheritance"}, {"key": "mitochondrial", "index": 9, "label": "", "clinvar": "Mitochondrial inheritance"}, {"key": "oligogenic", "index": 10, "label": "", "clinvar": "Oligogenic inheritance"}, {"key": "somatic", "index": 11, "label": "", "clinvar": "Somatic mutation"}, {"key": "unknown", "index": 12, "label": "", "clinvar": "Unknown mechanism"}, {"key": "other", "index": 13, "label": "", "clinvar": "Other"}, {"key": "digenic_recessive", "index": 14, "label": ""}, {"key": "digenic_dominant", "index": 15, "label": ""}, {"key": "isolated_cases", "index": 16, "label": ""}, {"key": "multifactorial", "index": 17, "label": "", "clinvar": "Multifactorial"}, {"key": "imprinting", "index": 18, "label": ""}]'
WHERE key='mode_of_inheritance'
and jsonb_array_length(options) < 19

[davmlaw]

As well as new "semidominant_inheritance" - there are entries in Emma's list that are not in 'clinvar' in EKey list:

{'Autosomal dominant inheritance with maternal imprinting',
 'Autosomal dominant inheritance with paternal imprinting',
 'Codominant',
 'Genetic anticipation',
 'Multifactorial inheritance',
 'Sporadic'}

We have multifactorial => ClinVar: "Multifactorial" which doesn't match Emma's above change just the clinvar entry? And also perhaps "isolated_cases" = ClinVar "Sporatic"?

Should we add all of these?

[TheMadBug]

Note that the labels don't need to line up directly e.g. this is in mode_of_inheritance:

  {
    "key": "x_linked_recessive",
    "index": 6,
    "label": "",
    "clinvar": "X-linked recessive inheritance"
  },

Probably should future proof by adding the rest, but I wouldn't worry about it as a priority until it's requested.

[davmlaw]

Our entry for multifactorial has clinvar = "Multifactorial" while the correct ClinVar entry according to Emma is 'Multifactorial inheritance'

[TheMadBug]

That should def be fixed, will work on an upgrade script.

[davmlaw]

James to make upgrade script with semi-dominant and clinvar multifactorial