rs2304167

Positions:

chr19-55015713-C-T

Variant summary

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

The NM_001083899.2(GP6):c.745G>A(p.Ala249Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,565,964 control chromosomes in the GnomAD database, including 508,174 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 0.74 ( 43220 hom., cov: 30)

Exomes 𝑓: 0.81 ( 464954 hom. )

Consequence

GP6
NM_001083899.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.77

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=1.0152187E-6).

BP6

Variant 19-55015713-C-T is Benign according to our data. Variant chr19-55015713-C-T is described in ClinVar as [Benign]. Clinvar id is 257424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55015713-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GP6	NM_001083899.2 link	c.745G>A	p.Ala249Thr	missense_variant	7/8	ENST00000310373.7	NP_001077368.2	Q9HCN6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7 link	c.745G>A	p.Ala249Thr	missense_variant	7/8	1	NM_001083899.2	ENSP00000308782.3		Q9HCN6-3
GP6	ENST00000417454.5 link	c.745G>A	p.Ala249Thr	missense_variant	7/8	1		ENSP00000394922.1		Q9HCN6-1

Frequencies

GnomAD3 genomes

AF:

0.742

AC:

112611

AN:

151798

Hom.:

43216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.799

Gnomad ASJ

AF:

0.792

Gnomad EAS

AF:

0.822

Gnomad SAS

AF:

0.721

Gnomad FIN

AF:

0.876

Gnomad MID

AF:

0.842

Gnomad NFE

AF:

0.832

Gnomad OTH

AF:

0.783

GnomAD3 exomes

AF:

0.797

AC:

198230

AN:

248688

Hom.:

80048

AF XY:

0.797

AC XY:

107483

AN XY:

134862

show subpopulations

Gnomad AFR exome

AF:

0.506

Gnomad AMR exome

AF:

0.830

Gnomad ASJ exome

AF:

0.797

Gnomad EAS exome

AF:

0.835

Gnomad SAS exome

AF:

0.727

Gnomad FIN exome

AF:

0.871

Gnomad NFE exome

AF:

0.825

Gnomad OTH exome

AF:

0.810

GnomAD4 exome

AF:

0.808

AC:

1143233

AN:

1414048

Hom.:

464954

Cov.:

AF XY:

0.808

AC XY:

571058

AN XY:

706660

show subpopulations

Gnomad4 AFR exome

AF:

0.509

Gnomad4 AMR exome

AF:

0.825

Gnomad4 ASJ exome

AF:

0.795

Gnomad4 EAS exome

AF:

0.806

Gnomad4 SAS exome

AF:

0.731

Gnomad4 FIN exome

AF:

0.871

Gnomad4 NFE exome

AF:

0.821

Gnomad4 OTH exome

AF:

0.796

GnomAD4 genome

AF:

0.742

AC:

112658

AN:

151916

Hom.:

43220

Cov.:

AF XY:

0.745

AC XY:

55329

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.522

Gnomad4 AMR

AF:

0.799

Gnomad4 ASJ

AF:

0.792

Gnomad4 EAS

AF:

0.821

Gnomad4 SAS

AF:

0.721

Gnomad4 FIN

AF:

0.876

Gnomad4 NFE

AF:

0.832

Gnomad4 OTH

AF:

0.781

Alfa

AF:

0.810

Hom.:

92965

Bravo

AF:

0.727

TwinsUK

AF:

0.821

AC:

3043

ALSPAC

AF:

0.817

AC:

3147

ESP6500AA

AF:

0.524

AC:

2097

ESP6500EA

AF:

0.830

AC:

6939

ExAC

AF:

0.788

AC:

95263

Asia WGS

AF:

0.748

AC:

2601

AN:

3478

EpiCase

AF:

0.824

EpiControl

AF:

0.827

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Platelet-type bleeding disorder 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.57

DANN

Benign

0.64

DEOGEN2

Benign

0.026

T;.;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.012

MetaRNN

Benign

0.0000010

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.90

L;L;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.040

N;N;N

REVEL

Benign

0.011

Sift

Benign

0.98

T;T;T

Sift4G

Benign

0.40

T;D;T

Polyphen

0.0010

B;B;B

Vest4

0.015

MPC

0.19

ClinPred

0.0048

GERP RS

-6.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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