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]

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Variant: NM_007373.4(SHOC2):c.170C>T (p.Ser57Phe)

CA185080

179760 (ClinVar)

Gene: SHOC2

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6b2642de-1576-44fc-ad42-04b45dae029d

Approved on: 2020-07-23

Published on: 2020-07-28

HGVS expressions

NM_007373.4:c.170C>T

NM_007373.4(SHOC2):c.170C>T (p.Ser57Phe)

NC_000010.11:g.110964528C>T

CM000672.2:g.110964528C>T

NC_000010.10:g.112724286C>T

CM000672.1:g.112724286C>T

NC_000010.9:g.112714276C>T

NG_028922.1:g.49986C>T

NM_001269039.1:c.170C>T

NM_007373.3:c.170C>T

NM_001269039.2:c.170C>T

NM_001324336.1:c.170C>T

NM_001324337.1:c.170C>T

NR_136749.1:n.116-21100C>T

ENST00000265277.9:c.170C>T

ENST00000369452.8:c.170C>T

ENST00000489390.1:n.56-35887C>T

ENST00000489783.1:n.548C>T

Uncertain Significance

PP2

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.170C>T (p.Ser57Phe) variant in SHOC2 was present in 0.0055% (5/35376 CI 95%) of Latino alleles in gnomAD v2.1.1 (BS1 not met; PMID: 29493581). It has been identified in healthy individuals without clinical features of a RASopathy, but this information does not meet the current criteria to apply BS2 (Ambry Genetics internal data, Baylor Genetics internal data). The variant is located in SHOC2, 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.Ser57Phe variant is uncertain. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): PP2.

PP2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

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