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

Variant: NM_007373.3(SHOC2):c.10A>C (p.Ser4Arg)

CA136657

40635 (ClinVar)

Gene: SHOC2

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f8ec95a4-b09f-4a17-984e-06b4098449c2

HGVS expressions

NM_007373.3:c.10A>C

NM_007373.3(SHOC2):c.10A>C (p.Ser4Arg)

NM_001269039.1:c.10A>C

NM_001269039.2:c.10A>C

NM_001324336.1:c.10A>C

NM_001324337.1:c.10A>C

NR_136749.1:n.116-21260A>C

ENST00000265277.9:c.10A>C

ENST00000369452.8:c.10A>C

ENST00000480155.1:n.494A>C

ENST00000489390.1:n.56-36047A>C

ENST00000489783.1:n.388A>C

NC_000010.11:g.110964368A>C

CM000672.2:g.110964368A>C

NC_000010.10:g.112724126A>C

CM000672.1:g.112724126A>C

NC_000010.9:g.112714116A>C

NG_028922.1:g.49826A>C

Benign

BA1 BP5

BP2

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.10A>C variant in SHOC2 has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx, Partners LMM GTR Lab ID: 26957, 21766 internal data; ClinVar SCV000209046.7, SCV000062455.5). The filtering allele frequency of the c.10A>C (p.Ser4Arg) variant is 0.356% for Latino chromosomes by the Exome Aggregation Consortium (49/10712 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1). In summary, this variant meets criteria to be classified as benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BA1, BP5.

BA1

The allele frequency of the p.Ser4Arg variant is 0.46% (49/10712) of Latino chromosomes by the Exome Aggregation Consortium (http://exac.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel for autosomal dominant RASopathy variants (BA1).

BP5

The variant has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx, Partners LMM GTR Lab ID: 26957, 21766 internal data; ClinVar SCV000209046.7, SCV000062455.5).

BP2

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

Approved on: 2017-04-03

Published on: 2018-12-10

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