19-55014735-GCAGACAGA-GCAGACAGACAGACAGA
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
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. Synonymous variant affecting the same amino acid position (i.e. L403L) has been classified as Likely benign.
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
Publications
5 publications found
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 was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001083899.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GP6 | NM_016363.5 | MANE Select | c.*178_*185dupTCTGTCTG | 3_prime_UTR | Exon 8 of 8 | NP_057447.5 | Q9HCN6-1 | ||
| GP6 | NM_001083899.2 | c.1202_1209dupTCTGTCTG | p.Pro404SerfsTer7 | frameshift | Exon 8 of 8 | NP_001077368.2 | Q9HCN6-3 | ||
| GP6 | NM_001256017.2 | c.*178_*185dupTCTGTCTG | 3_prime_UTR | Exon 7 of 7 | NP_001242946.2 | Q9HCN6-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GP6 | ENST00000310373.7 | TSL:1 | c.1202_1209dupTCTGTCTG | p.Pro404SerfsTer7 | frameshift | Exon 8 of 8 | ENSP00000308782.3 | Q9HCN6-3 | |
| GP6 | ENST00000417454.5 | TSL:1 MANE Select | c.*178_*185dupTCTGTCTG | 3_prime_UTR | Exon 8 of 8 | ENSP00000394922.1 | Q9HCN6-1 | ||
| GP6 | ENST00000333884.2 | TSL:1 | c.*178_*185dupTCTGTCTG | 3_prime_UTR | Exon 7 of 7 | ENSP00000334552.2 | Q9HCN6-2 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152006Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152006
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000405 AC: 1AN: 247204 AF XY: 0.00000746 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
247204
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461408Hom.: 0 Cov.: 39 AF XY: 0.00000275 AC XY: 2AN XY: 726984 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1461408
Hom.:
Cov.:
39
AF XY:
AC XY:
2
AN XY:
726984
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33468
American (AMR)
AF:
AC:
0
AN:
44644
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26042
East Asian (EAS)
AF:
AC:
1
AN:
39652
South Asian (SAS)
AF:
AC:
0
AN:
86162
European-Finnish (FIN)
AF:
AC:
0
AN:
53410
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111880
Other (OTH)
AF:
AC:
0
AN:
60382
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
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50-55
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>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152124Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74370 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152124
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74370
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41498
American (AMR)
AF:
AC:
0
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5140
South Asian (SAS)
AF:
AC:
1
AN:
4822
European-Finnish (FIN)
AF:
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67992
Other (OTH)
AF:
AC:
0
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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