1-21864191-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP2PP3
The NM_005529.7(HSPG2):c.4649G>A(p.Arg1550His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000773 in 1,552,590 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. R1550C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005529.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPG2 | NM_005529.7 | c.4649G>A | p.Arg1550His | missense_variant | 37/97 | ENST00000374695.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPG2 | ENST00000374695.8 | c.4649G>A | p.Arg1550His | missense_variant | 37/97 | 1 | NM_005529.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000189 AC: 3AN: 158730Hom.: 0 AF XY: 0.0000239 AC XY: 2AN XY: 83676
GnomAD4 exome AF: 0.00000714 AC: 10AN: 1400390Hom.: 0 Cov.: 31 AF XY: 0.0000116 AC XY: 8AN XY: 690914
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74356
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 27, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2020 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with HSPG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 447553). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with histidine at codon 1550 of the HSPG2 protein (p.Arg1550His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 19, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at