Variant 19-55014735-GCAGACAGA-GCAGACAGACAGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 4P and 16B. PVS1_StrongBP6_Very_StrongBA1

The NM_001083899.2(GP6):c.1206_1209dupTCTG(p.Pro404SerfsTer61) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 1,613,468 control chromosomes in the GnomAD database, including 1,636 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 291 hom., cov: 31)

Exomes 𝑓: 0.031 ( 1345 hom. )

Consequence

GP6
NM_001083899.2 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.173

Variant links:

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]

GP6 links:

GP6-AS1 (HGNC:55305): (GP6 antisense RNA 1)

GP6-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 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.

BP6

Variant 19-55014735-G-GCAGA is Benign according to our data. Variant chr19-55014735-G-GCAGA is described in ClinVar as [Benign]. Clinvar id is 257410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_001083899.2 link	c.1206_1209dupTCTG	p.Pro404SerfsTer61	frameshift_variant	Exon 8 of 8	ENST00000310373.7	NP_001077368.2	Q9HCN6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7 link	c.1206_1209dupTCTG	p.Pro404SerfsTer61	frameshift_variant	Exon 8 of 8	1	NM_001083899.2	ENSP00000308782.3		Q9HCN6-3
GP6	ENST00000417454 link	c.182_185dupTCTG		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000394922.1		Q9HCN6-1

Frequencies

GnomAD3 genomes

AF:

0.0469

AC:

7123

AN:

151980

Hom.:

291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0784

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0786

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.0651

Gnomad FIN

AF:

0.0155

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0194

Gnomad OTH

AF:

0.0350

GnomAD3 exomes

AF:

0.0467

AC:

11550

AN:

247204

Hom.:

434

AF XY:

0.0439

AC XY:

5883

AN XY:

134012

show subpopulations

Gnomad AFR exome

AF:

0.0784

Gnomad AMR exome

AF:

0.0907

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.145

Gnomad SAS exome

AF:

0.0604

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.0197

Gnomad OTH exome

AF:

0.0327

GnomAD4 exome

AF:

0.0308

AC:

44944

AN:

1461370

Hom.:

1345

Cov.:

AF XY:

0.0309

AC XY:

22465

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.0816

Gnomad4 AMR exome

AF:

0.0892

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.0585

Gnomad4 FIN exome

AF:

0.0138

Gnomad4 NFE exome

AF:

0.0208

Gnomad4 OTH exome

AF:

0.0350

GnomAD4 genome

AF:

0.0469

AC:

7137

AN:

152098

Hom.:

291

Cov.:

AF XY:

0.0474

AC XY:

3526

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0783

Gnomad4 AMR

AF:

0.0787

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.0649

Gnomad4 FIN

AF:

0.0155

Gnomad4 NFE

AF:

0.0194

Gnomad4 OTH

AF:

0.0374

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 03, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over