2-151664532-G-C
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM5
The NM_001164507.2(NEB):c.5420C>G(p.Ala1807Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1807P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
Publications
- nemaline myopathy 2Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P, Ambry Genetics
- childhood-onset nemaline myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- intermediate nemaline myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- typical nemaline myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- lethal multiple pterygium syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- severe congenital nemaline myopathyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.5420C>G | p.Ala1807Gly | missense_variant | Exon 44 of 182 | 5 | NM_001164508.2 | ENSP00000380505.3 | ||
NEB | ENST00000427231.7 | c.5420C>G | p.Ala1807Gly | missense_variant | Exon 44 of 182 | 5 | NM_001164507.2 | ENSP00000416578.2 | ||
NEB | ENST00000409198.5 | c.5420C>G | p.Ala1807Gly | missense_variant | Exon 44 of 150 | 5 | ENSP00000386259.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1807 of the NEB protein (p.Ala1807Gly). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with clinical features of nemaline myopathy (Invitae). This variant is not present in population databases (gnomAD no frequency). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at