chr2-85553488-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000821.7(GGCX):c.899C>T(p.Ser300Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,534 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000821.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000811 AC: 2AN: 246754Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 133988
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461318Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 726914
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74362
ClinVar
Submissions by phenotype
Body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency Pathogenic:1
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not provided Uncertain:1
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. Experimental studies have shown that this missense change affects GGCX function (PMID: 33507293, 34816548). 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"). ClinVar contains an entry for this variant (Variation ID: 16196). This missense change has been observed in individual(s) with clinical features of GGCX-related conditions (PMID: 18800149). This variant is present in population databases (rs121909684, gnomAD 0.03%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 300 of the GGCX protein (p.Ser300Phe). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at