1-21876514-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005529.7(HSPG2):āc.2824C>Gā(p.Gln942Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_005529.7 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250710Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135650
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461794Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727192
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74360
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 06, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 21, 2024 | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 942 of the HSPG2 protein (p.Gln942Glu). This variant is present in population databases (rs377203405, gnomAD 0.0009%). 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: 447547). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at