rs1613662

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001083899.2(GP6):c.655C>T(p.Pro219Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 1,541,374 control chromosomes in the GnomAD database, including 544,761 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 53189 hom., cov: 31)

Exomes 𝑓: 0.84 ( 491572 hom. )

Consequence

GP6
NM_001083899.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.373

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3788144E-6).

BP6

Variant 19-55025227-G-A is Benign according to our data. Variant chr19-55025227-G-A is described in ClinVar as [Benign]. Clinvar id is 257422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55025227-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GP6	NM_001083899.2 linkuse as main transcript	c.655C>T	p.Pro219Ser	missense_variant	5/8	ENST00000310373.7	NP_001077368.2
GP6-AS1	XR_001754012.3 linkuse as main transcript	n.122-17573G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7 linkuse as main transcript	c.655C>T	p.Pro219Ser	missense_variant	5/8	1	NM_001083899.2	ENSP00000308782		Q9HCN6-3
GP6-AS1	ENST00000593060.5 linkuse as main transcript	n.156-17573G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.834

AC:

126869

AN:

152052

Hom.:

53163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.774

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.887

Gnomad ASJ

AF:

0.795

Gnomad EAS

AF:

0.976

Gnomad SAS

AF:

0.787

Gnomad FIN

AF:

0.890

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.846

Gnomad OTH

AF:

0.846

GnomAD3 exomes

AF:

0.854

AC:

133645

AN:

156582

Hom.:

57422

AF XY:

0.848

AC XY:

70132

AN XY:

82720

show subpopulations

Gnomad AFR exome

AF:

0.763

Gnomad AMR exome

AF:

0.922

Gnomad ASJ exome

AF:

0.796

Gnomad EAS exome

AF:

0.981

Gnomad SAS exome

AF:

0.789

Gnomad FIN exome

AF:

0.886

Gnomad NFE exome

AF:

0.840

Gnomad OTH exome

AF:

0.842

GnomAD4 exome

AF:

0.840

AC:

1167289

AN:

1389204

Hom.:

491572

Cov.:

AF XY:

0.840

AC XY:

575866

AN XY:

685906

show subpopulations

Gnomad4 AFR exome

AF:

0.764

Gnomad4 AMR exome

AF:

0.918

Gnomad4 ASJ exome

AF:

0.794

Gnomad4 EAS exome

AF:

0.981

Gnomad4 SAS exome

AF:

0.790

Gnomad4 FIN exome

AF:

0.884

Gnomad4 NFE exome

AF:

0.838

Gnomad4 OTH exome

AF:

0.840

GnomAD4 genome

AF:

0.834

AC:

126955

AN:

152170

Hom.:

53189

Cov.:

AF XY:

0.839

AC XY:

62391

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.773

Gnomad4 AMR

AF:

0.887

Gnomad4 ASJ

AF:

0.795

Gnomad4 EAS

AF:

0.976

Gnomad4 SAS

AF:

0.786

Gnomad4 FIN

AF:

0.890

Gnomad4 NFE

AF:

0.846

Gnomad4 OTH

AF:

0.845

Alfa

AF:

0.841

Hom.:

117927

Bravo

AF:

0.832

TwinsUK

AF:

0.837

AC:

3105

ALSPAC

AF:

0.836

AC:

3223

ESP6500AA

AF:

0.779

AC:

2935

ESP6500EA

AF:

0.847

AC:

6850

ExAC

AF:

0.765

AC:

61765

Asia WGS

AF:

0.884

AC:

3076

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 31699788, 11571236, 22133274, 19786296, 25525159, 20227257, 21232005, 20723028, 18349091, 19278955) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Platelet-type bleeding disorder 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.39

DANN

Benign

0.25

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0023

MetaRNN

Benign

0.0000014

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.11

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

0.18

N;N

REVEL

Benign

0.0080

Sift

Benign

0.76

T;T

Sift4G

Benign

0.91

T;T

Polyphen

0.0

B;B

Vest4

0.095

MPC

0.16

ClinPred

0.00058

GERP RS

-0.22

Varity_R

0.021

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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