rs188987688
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBS1_Supporting
The NM_005529.7(HSPG2):c.8288G>A(p.Arg2763His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R2763C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005529.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HSPG2 | NM_005529.7 | c.8288G>A | p.Arg2763His | missense_variant | 63/97 | ENST00000374695.8 | NP_005520.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HSPG2 | ENST00000374695.8 | c.8288G>A | p.Arg2763His | missense_variant | 63/97 | 1 | NM_005529.7 | ENSP00000363827.3 | ||
HSPG2 | ENST00000453796.1 | n.533G>A | non_coding_transcript_exon_variant | 3/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000171 AC: 43AN: 251174Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135842
GnomAD4 exome AF: 0.0000589 AC: 86AN: 1461314Hom.: 0 Cov.: 32 AF XY: 0.0000454 AC XY: 33AN XY: 726984
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74504
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 05, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 19, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2763 of the HSPG2 protein (p.Arg2763His). This variant is present in population databases (rs188987688, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with HSPG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 198333). 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 tolerated. 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 19, 2016 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2022 | The c.8288G>A (p.R2763H) alteration is located in exon 62 (coding exon 62) of the HSPG2 gene. This alteration results from a G to A substitution at nucleotide position 8288, causing the arginine (R) at amino acid position 2763 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at