rs751315560
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_005529.7(HSPG2):c.6516C>A(p.Asn2172Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPG2 | NM_005529.7 | c.6516C>A | p.Asn2172Lys | missense_variant | 51/97 | ENST00000374695.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPG2 | ENST00000374695.8 | c.6516C>A | p.Asn2172Lys | missense_variant | 51/97 | 1 | NM_005529.7 | P1 | |
HSPG2 | ENST00000493940.2 | n.274C>A | non_coding_transcript_exon_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250738Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135710
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1461428Hom.: 0 Cov.: 36 AF XY: 0.00000963 AC XY: 7AN XY: 727064
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 02, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 04, 2021 | This sequence change replaces asparagine with lysine at codon 2172 of the HSPG2 protein (p.Asn2172Lys). The asparagine residue is weakly conserved and there is a moderate physicochemical difference between asparagine and lysine. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with HSPG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 585999). This variant is present in population databases (rs751315560, ExAC 0.002%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at