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.78+1G>A

CA1912012

552018 (ClinVar)

Gene: NEB
Condition: nemaline myopathy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: a75b11b3-92c0-4118-8375-f87306c34762
Approved on: 2024-08-07
Published on: 2024-10-01

HGVS expressions

NM_001164508.2:c.78+1G>A
NM_001164508.2(NEB):c.78+1G>A
NC_000002.12:g.151729614C>T
CM000664.2:g.151729614C>T
NC_000002.11:g.152586128C>T
CM000664.1:g.152586128C>T
NC_000002.10:g.152294374C>T
NG_009382.2:g.9874G>A
ENST00000397345.8:c.78+1G>A
ENST00000427231.7:c.78+1G>A
ENST00000172853.14:c.78+1G>A
ENST00000397345.7:c.78+1G>A
ENST00000409198.5:c.78+1G>A
ENST00000427231.6:c.78+1G>A
ENST00000603639.5:c.78+1G>A
ENST00000604864.5:c.78+1G>A
ENST00000618972.4:c.78+1G>A
NM_001164507.1:c.78+1G>A
NM_001164508.1:c.78+1G>A
NM_001271208.1:c.78+1G>A
NM_004543.4:c.78+1G>A
NM_001271208.2:c.78+1G>A
NM_004543.5:c.78+1G>A
NM_001164507.2:c.78+1G>A
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Pathogenic

Met criteria codes 2
PVS1 PM3_Very Strong
Not Met criteria codes 3
PM2 BA1 BS1

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.78+1G>A variant in NEB occurs within the canonical splice donor site +1 of intron 4. It is expected to disrupt RNA splicing of in-frame exon 4 leading to loss of protein function and loss-of-function of NEB is an established disease mechanism (PVS1). The highest population minor allele frequency in gnomAD v4.1.0 is 0.00007461 (88/1179410) in non-Finnish European which does not meet the threshold for PM2_Supporting (≤ 0.0000559). This variant has been detected in more than four unrelated affected individuals with a second pathogenic variant (PM3_Very Strong, Internal lab contributor: Invitae, SCV001578888.4; PMID: 25205138, 30859559). 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_Strong, PM3_Very Strong (Congenital Myopathies VCEP specifications version 1; 8/7/2024).
Met criteria codes
PVS1
The c.78+1G>A variant in NEB occurs within the canonical splice donor site +1 of intron 4. It is expected to disrupt RNA splicing of in-frame exon 4 leading to loss of protein function and loss-of-function of NEB is an established disease mechanism (PVS1)
PM3_Very Strong
Detected in more than four unrelated affected individuals with a second pathogenic variant (PM3_Very Strong, Internal lab contributor: Invitae, SCV001578888.4; PMID: 25205138, 30859559)
Not Met criteria codes
PM2
The gnomAD v4.1.0 highest population MAF is 0.00007461 (88/1179410) in non-Finnish European which does not meet the threshold for PM2_P (≤ 0.0000559)
BA1
The gnomAD v4.1.0 highest population MAF is 0.00007461 (88/1179410) in non-Finnish European which does not meet the threshold for PM2_P/BA1/BS1
BS1
The gnomAD v4.1.0 highest population MAF is 0.00007461 (88/1179410) in non-Finnish European which does not meet the threshold for PM2_P/BA1/BS1
Curation History
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