chr2-219283441-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006736.6(DNAJB2):c.571C>T(p.Arg191Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R191Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_006736.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAJB2 | NM_006736.6 | c.571C>T | p.Arg191Trp | missense_variant | 8/9 | ENST00000336576.10 | |
DNAJB2 | NM_001039550.2 | c.571C>T | p.Arg191Trp | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAJB2 | ENST00000336576.10 | c.571C>T | p.Arg191Trp | missense_variant | 8/9 | 1 | NM_006736.6 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000598 AC: 15AN: 250866Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135650
GnomAD4 exome AF: 0.0000527 AC: 77AN: 1461784Hom.: 0 Cov.: 32 AF XY: 0.0000509 AC XY: 37AN XY: 727190
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74312
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 28, 2022 | The c.571C>T (p.R191W) alteration is located in exon 8 (coding exon 7) of the DNAJB2 gene. This alteration results from a C to T substitution at nucleotide position 571, causing the arginine (R) at amino acid position 191 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Neuronopathy, distal hereditary motor, autosomal recessive 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 191 of the DNAJB2 protein (p.Arg191Trp). This variant is present in population databases (rs776893562, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with DNAJB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 473304). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at