rs140139732
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_005529.7(HSPG2):c.12220C>T(p.Arg4074Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,551,072 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4074H) has been classified as Uncertain significance.
Frequency
Consequence
NM_005529.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPG2 | NM_005529.7 | c.12220C>T | p.Arg4074Cys | missense_variant | 88/97 | ENST00000374695.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPG2 | ENST00000374695.8 | c.12220C>T | p.Arg4074Cys | missense_variant | 88/97 | 1 | NM_005529.7 | P1 | |
HSPG2 | ENST00000486901.1 | n.1559C>T | non_coding_transcript_exon_variant | 2/11 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00296 AC: 450AN: 152120Hom.: 7 Cov.: 33
GnomAD3 exomes AF: 0.00337 AC: 525AN: 155730Hom.: 8 AF XY: 0.00307 AC XY: 252AN XY: 82100
GnomAD4 exome AF: 0.00175 AC: 2447AN: 1398834Hom.: 13 Cov.: 33 AF XY: 0.00169 AC XY: 1169AN XY: 690000
GnomAD4 genome ? AF: 0.00296 AC: 450AN: 152238Hom.: 7 Cov.: 33 AF XY: 0.00439 AC XY: 327AN XY: 74446
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 23, 2021 | This variant is associated with the following publications: (PMID: 25504735) - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 05, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Lethal Kniest-like syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 16, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
HSPG2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 18, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Schwartz-Jampel syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 16, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Connective tissue disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Aug 18, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at