chr1-21842350-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS1
The NM_005529.7(HSPG2):c.8941G>A(p.Val2981Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,609,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Consequence
NM_005529.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPG2 | NM_005529.7 | c.8941G>A | p.Val2981Ile | missense_variant | 68/97 | ENST00000374695.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPG2 | ENST00000374695.8 | c.8941G>A | p.Val2981Ile | missense_variant | 68/97 | 1 | NM_005529.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00106 AC: 161AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000272 AC: 67AN: 246378Hom.: 0 AF XY: 0.000202 AC XY: 27AN XY: 133728
GnomAD4 exome AF: 0.000102 AC: 149AN: 1457630Hom.: 0 Cov.: 34 AF XY: 0.0000801 AC XY: 58AN XY: 724544
GnomAD4 genome AF: 0.00106 AC: 161AN: 152300Hom.: 0 Cov.: 33 AF XY: 0.00106 AC XY: 79AN XY: 74474
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 30, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 02, 2023 | The HSPG2 c.8941G>A; p.Val2981Ile variant (rs2229490), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 289426). This variant is found in the African population with an allele frequency of 0.3% (76/24,484 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is neutral (REVEL: 0.033). While the high population frequency suggests that this is likely a benign variant, given the lack of clinical and functional data, the significance of this variant is uncertain at this time. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at