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_001040142.2(SCN2A):c.2723A>G (p.Lys908Arg)

CA155058

130219 (ClinVar)

Gene: SCN2A

Condition: complex neurodevelopmental disorder

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: fe35e1e4-1642-4c1a-af70-afe80080d0ed

Approved on: 2024-05-09

Published on: 2024-05-09

HGVS expressions

NM_001040142.2:c.2723A>G

NM_001040142.2(SCN2A):c.2723A>G (p.Lys908Arg)

NC_000002.12:g.165344715A>G

CM000664.2:g.165344715A>G

NC_000002.11:g.166201225A>G

CM000664.1:g.166201225A>G

NC_000002.10:g.165909471A>G

NG_008143.1:g.110314A>G

ENST00000631182.3:c.2723A>G

ENST00000375437.7:c.2723A>G

ENST00000636071.2:c.2723A>G

ENST00000636135.1:c.*1042A>G

ENST00000636384.2:c.*710A>G

ENST00000636662.2:c.*3246A>G

ENST00000636769.1:c.*665A>G

ENST00000636985.2:c.2327A>G

ENST00000637266.2:c.2723A>G

ENST00000673831.1:c.161A>G

ENST00000673883.1:c.161A>G

ENST00000674133.1:c.574A>G

ENST00000283256.10:c.2723A>G

ENST00000375427.4:c.2723A>G

ENST00000375437.6:c.2723A>G

ENST00000480032.4:n.2866A>G

ENST00000631182.2:c.2723A>G

NM_001040142.1:c.2723A>G

NM_001040143.1:c.2723A>G

NM_021007.2:c.2723A>G

NM_001040143.2:c.2723A>G

NM_001371246.1:c.2723A>G

NM_001371247.1:c.2723A>G

NM_021007.3:c.2723A>G

Benign

BA1 BS2

Evidence Links 0

Expert Panel

Epilepsy Sodium Channel VCEP

Criteria Specification Information

Criteria Specification: ClinGen Epilepsy Sodium Channel Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SCN2A Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Epilepsy Sodium Channel VCEP

The c.2723A>G variant in SCN2A is a missense variant predicted to cause substitution of lysine by arginine at amino acid 908 (p.Lys908Arg). This variant is present in gnomAD v2.1 at an allele frequency of 0.4% (1190/282874 alleles), with the highest sub-population minor allele frequency of 0.6% in the European (non-Finnish) population, which exceeds the ClinGen Epilepsy Sodium Channel threshold (0.01%) for BA1. Additionally, gnomAD v2.1.1 reports 7 individuals with this variant in a homozygous state (BS1). In summary, this variant meets the criteria to be classified as Benign for AUTOSOMAL DOMINANT COMPLEX NEURODEVELOPMENTAL DISORDER based on the ACMG/AMP criteria applied, as specified by the ClinGen Epilepsy Sodium Channel VCEP: BA1, BS1 (VCEP specifications version 1.0; 6/13/2023)

BA1

Guidance from the Epilepsy Sodium Channel Expert panel identifies an allele frequency of greater than or equal to 0.01% as meeting this criteria. The c.2723A>G variant has an allele frequency of 0.6%

BS2

GnomAD v2.1.1 reports 7 individuals with this variant in a homozygous state.

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