19-55014735-GCAGACAGA-GCAGACAGACAGACAGA
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_001083899.2(GP6):c.1202_1209dupTCTGTCTG(p.Pro404SerfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,532 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
GP6
NM_001083899.2 frameshift
NM_001083899.2 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.173
Genes affected
GP6 (HGNC:14388): (glycoprotein VI platelet) This gene encodes a platelet membrane glycoprotein of the immunoglobulin superfamily. The encoded protein is a receptor for collagen and plays a critical role in collagen-induced platelet aggregation and thrombus formation. The encoded protein forms a complex with the Fc receptor gamma-chain that initiates the platelet activation signaling cascade upon collagen binding. Mutations in this gene are a cause of platelet-type bleeding disorder-11 (BDPLT11). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.351 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GP6 | ENST00000310373.7 | c.1202_1209dupTCTGTCTG | p.Pro404SerfsTer7 | frameshift_variant | Exon 8 of 8 | 1 | NM_001083899.2 | ENSP00000308782.3 | ||
GP6 | ENST00000417454 | c.*178_*185dupTCTGTCTG | 3_prime_UTR_variant | Exon 8 of 8 | 1 | ENSP00000394922.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152006Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000405 AC: 1AN: 247204Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134012
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461408Hom.: 0 Cov.: 39 AF XY: 0.00000275 AC XY: 2AN XY: 726984
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152124Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74370
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at