rs376303676
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM5PP2PP3BS2
The NM_006182.4(DDR2):c.757G>A(p.Gly253Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. G253C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_006182.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DDR2 | NM_006182.4 | c.757G>A | p.Gly253Ser | missense_variant | 8/18 | ENST00000367921.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DDR2 | ENST00000367921.8 | c.757G>A | p.Gly253Ser | missense_variant | 8/18 | 1 | NM_006182.4 | P1 | |
DDR2 | ENST00000367922.7 | c.757G>A | p.Gly253Ser | missense_variant | 9/19 | 1 | P1 | ||
DDR2 | ENST00000446985.6 | c.757G>A | p.Gly253Ser | missense_variant | 8/18 | 3 | P1 | ||
DDR2 | ENST00000672207.1 | n.1143G>A | non_coding_transcript_exon_variant | 8/13 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251152Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135698
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461868Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 727236
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74334
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 26, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 253 of the DDR2 protein (p.Gly253Ser). This variant is present in population databases (rs376303676, gnomAD 0.003%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with DDR2-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at