Genetic Variant GP6:p.Pro404SerfsTer61 (chr19-55014735-G-GCAGA) – ACMG Classification: Benign (-12 pts)

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

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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.

19-55014735-GCAGACAGA-GCAGACAGACAGA

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