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]

Variant: NM_001164508.2(NEB):c.18783G>A (p.Gln6261=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA203801

199224 (ClinVar)

Gene: NEB

Condition: nemaline myopathy

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 4360d3e6-1e78-421b-9836-b4a6da3918e9

Approved on: 2024-08-07

Published on: 2024-10-01

HGVS expressions

NM_001164508.2:c.18783G>A

NM_001164508.2(NEB):c.18783G>A (p.Gln6261=)

NC_000002.12:g.151562719C>T

CM000664.2:g.151562719C>T

NC_000002.11:g.152419233C>T

CM000664.1:g.152419233C>T

NC_000002.10:g.152127479C>T

NG_009382.2:g.176769G>A

ENST00000690043.1:c.1634G>A

ENST00000397345.8:c.18783G>A

ENST00000427231.7:c.18783G>A

ENST00000172853.14:c.13680G>A

ENST00000397345.7:c.18783G>A

ENST00000409198.5:c.13680G>A

ENST00000413693.5:c.2973G>A

ENST00000427231.6:c.18783G>A

ENST00000603639.5:c.18783G>A

ENST00000604864.5:c.18783G>A

ENST00000618972.4:c.18783G>A

NM_001164507.1:c.18783G>A

NM_001164508.1:c.18783G>A

NM_001271208.1:c.18783G>A

NM_004543.4:c.13680G>A

NM_001271208.2:c.18783G>A

NM_004543.5:c.13680G>A

NM_001164507.2:c.18783G>A

Benign

BA1

BS1 BP4 BP7 PM2

Evidence Links 0

Expert Panel

Congenital Myopathies VCEP

Criteria Specification Information

Criteria Specification: ClinGen Congenital Myopathies Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for NEB Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Congenital Myopathies VCEP

The c.18783G>A is a synonymous (silent) variant (p.Gln6261=) that is not predicted by SpliceAI to impact splicing. However, it occurs at a nucleotide that is conserved as shown by the UCSC Genome Browser (BP4, BP7 not met). The highest population filtering allele frequency in gnomAD v4.1.0 is 0.02590 (2413/89448 alleles, 58 homozygotes) in the South Asian population, which is higher than the ClinGen Congenital Myopathies threshold (≥0.00559) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as benign for autosomal recessive nemaline myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: BA1. (Congenital Myopathies VCEP specifications version 1; 8/7/2024)

BA1

The highest population filtering allele frequency in gnomAD v4.1.0 is 0.02590 (2413/89448 alleles, 58 homozygotes) in the South Asian population, which is higher than the ClinGen Congenital Myopathies threshold (≥0.00559) for BA1, and therefore meets this criterion

BS1

The highest population filtering allele frequency in gnomAD v4.1.0 is 0.02590 (2413/89448 alleles, 58 homozygotes) in the South Asian population

BP4

The c.18783G>A (p.Gln6261=) is a silent variant that is not predicted by SpliceAI to impact splicing. However, it occurs at a nucleotide that is conserved as shown by the UCSC Genome Browser

BP7

The c.18783G>A (p.Gln6261=) is a silent variant that is not predicted by SpliceAI to impact splicing. However, it occurs at a nucleotide that is conserved as shown by the UCSC Genome Browser

PM2

The highest population filtering allele frequency in gnomAD v4.1.0 is 0.02590 (2413/89448 alleles, 58 homozygotes) in the South Asian population

Curation History

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