Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

CA378386067

Gene: SHOC2

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: cfe4649b-118d-4271-88f3-f0ef6ea17208

HGVS expressions

NR_136749.1:n.116-20704A>T

NC_000010.11:g.110964924A>T

CM000672.2:g.110964924A>T

NC_000010.10:g.112724682A>T

CM000672.1:g.112724682A>T

NC_000010.9:g.112714672A>T

NG_028922.1:g.50382A>T

NM_001269039.1:c.566A>T

NM_007373.3:c.566A>T

NM_001269039.2:c.566A>T

NM_001324336.1:c.566A>T

NM_001324337.1:c.566A>T

ENST00000265277.9:c.566A>T

ENST00000369452.8:c.566A>T

ENST00000451838.1:n.74A>T

ENST00000489390.1:n.56-35491A>T

Uncertain Significance

PS4_Supporting PP2 PM2

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.556A>T (p.Tyr189Phe) variant in the SHOC2 gene is absent from large population studies (PM2; gnomAD, http://gnomad.broadinstitute.org). The variant is located in the SHOC2 gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID: 29493581). In summary, the clinical significance of the p.Tyr189Phe variant is uncertain. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): PM2, PP2.

PS4_Supporting

3 year old male with speech delays, relative macrocephaly, hydronephrosis, and borderline short stature. He did not have classic facial gestalt of Noonan syndrome. He had a normal echocardiogram. Variant was also detected in the proband's mother who presented with short stature and mild hypertelorism. She had a normal echocardiogram. She had an unusual facial gestalt. No family history of loose anagen hair. Proband's hair wasn't easily pluckable. Neither individuals had a history of seizures.

PP2

The variant is located in the SHOC2 gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID: 29493581).

PM2

Variant is absent from gnomAD

Approved on: 2019-09-16

Published on: 2019-12-03

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