Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001164508.2(NEB):c.6937C>T (p.Arg2313Ter)

CA1909950

552042 (ClinVar)

Gene: NEB
Condition: nemaline myopathy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 80f75539-a010-47e2-9ba6-405747b28b4b
Approved on: 2024-09-16
Published on: 2024-10-01

HGVS expressions

NM_001164508.2:c.6937C>T
NM_001164508.2(NEB):c.6937C>T (p.Arg2313Ter)
NC_000002.12:g.151650864G>A
CM000664.2:g.151650864G>A
NC_000002.11:g.152507378G>A
CM000664.1:g.152507378G>A
NC_000002.10:g.152215624G>A
NG_009382.2:g.88624C>T
ENST00000397345.8:c.6937C>T
ENST00000427231.7:c.6937C>T
ENST00000172853.14:c.6937C>T
ENST00000397345.7:c.6937C>T
ENST00000409198.5:c.6937C>T
ENST00000427231.6:c.6937C>T
ENST00000603639.5:c.6937C>T
ENST00000604864.5:c.6937C>T
ENST00000618972.4:c.6937C>T
NM_001164507.1:c.6937C>T
NM_001164508.1:c.6937C>T
NM_001271208.1:c.6937C>T
NM_004543.4:c.6937C>T
NM_001271208.2:c.6937C>T
NM_004543.5:c.6937C>T
NM_001164507.2:c.6937C>T
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Pathogenic

Met criteria codes 3
PM3_Supporting PVS1 PM2_Supporting
Not Met criteria codes 3
BS1 BP2 BA1

Evidence Links 0

Expert Panel

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.6937C>T (p.Arg2313Ter) variant in NEB is a nonsense variant predicted to cause a premature stop codon in biologically-relevant exon 52/182 and to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). The highest population minor allele frequency in gnomAD v.4.1.0 is 0.00001669 (1/59924) in Admixed American which meets the threshold (MAF≤0.0000559) to apply PM2_Supporting. The variant was found in one proband with nemaline myopathy in the literature with a second nonsense variant identified in trans (PM3_Supporting, PMID: 25205138). In summary, this variant meets the criteria to be classified as pathogenic for autosomal recessive nemaline myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: PVS1, PM2_Supporting, PM3_Supporting (Congenital Myopathies VCEP specifications version 1; 09/16/2024)
Met criteria codes
PM3_Supporting
1 proband with unspecified form of nemaline myopathy was identified with this variant in a compound heterozygous state with another nonsense variant in trans (c.25176G>A, p.W8392*)(PMID:25205138)
PVS1
Nonsense variant predicted to undergo NMD and loss-of function is known mechanism of disease with multiple pathogenic/likely pathogenic variants reported 3' end of this variant (PMID: 25205138)
PM2_Supporting
The highest population minor allele frequency in gnomAD v4.1.0 is 0.00001669 (1/59924) in Admixed American which meets the threshold (MAF≤0.0000559) to apply PM2_ Supporting
Not Met criteria codes
BS1
The highest population minor allele frequency in gnomAD v4.1.0 is 0.00001669 (1/59924) in Admixed American which meets the threshold (MAF≤0.0000559) to apply PM2_ Supporting
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
The highest population minor allele frequency in gnomAD v4.1.0 is 0.00001669 (1/59924) in Admixed American which meets the threshold (MAF≤0.0000559) to apply PM2_ Supporting
Curation History
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