chr19-55014129-A-G

Variant names:

Variant summary

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

The NM_001083899.2(GP6):c.1816T>C(p.Phe606Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 690,984 control chromosomes in the GnomAD database, including 221,911 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 44359 hom., cov: 31)

Exomes 𝑓: 0.81 ( 177552 hom. )

Consequence

GP6
NM_001083899.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.84

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=1.0786426E-6).

BP6

Variant 19-55014129-A-G is Benign according to our data. Variant chr19-55014129-A-G is described in ClinVar as [Benign]. Clinvar id is 257416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
GP6	NM_001083899.2 link	c.1816T>C	p.Phe606Leu	missense_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.1816T>C	p.Phe606Leu	missense_variant	Exon 8 of 8	1	NM_001083899.2	ENSP00000308782.3		Q9HCN6-3
GP6	ENST00000417454 link	c.*792T>C		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000394922.1		Q9HCN6-1

Frequencies

GnomAD3 genomes

AF:

0.755

AC:

114725

AN:

151914

Hom.:

44351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.802

Gnomad ASJ

AF:

0.792

Gnomad EAS

AF:

0.825

Gnomad SAS

AF:

0.722

Gnomad FIN

AF:

0.876

Gnomad MID

AF:

0.842

Gnomad NFE

AF:

0.832

Gnomad OTH

AF:

0.789

GnomAD3 exomes

AF:

0.798

AC:

103813

AN:

130156

Hom.:

41873

AF XY:

0.795

AC XY:

56306

AN XY:

70860

show subpopulations

Gnomad AFR exome

AF:

0.563

Gnomad AMR exome

AF:

0.830

Gnomad ASJ exome

AF:

0.794

Gnomad EAS exome

AF:

0.837

Gnomad SAS exome

AF:

0.733

Gnomad FIN exome

AF:

0.870

Gnomad NFE exome

AF:

0.825

Gnomad OTH exome

AF:

0.808

GnomAD4 exome

AF:

0.809

AC:

435962

AN:

538952

Hom.:

177552

Cov.:

AF XY:

0.807

AC XY:

235572

AN XY:

292034

show subpopulations

Gnomad4 AFR exome

AF:

0.564

Gnomad4 AMR exome

AF:

0.825

Gnomad4 ASJ exome

AF:

0.797

Gnomad4 EAS exome

AF:

0.805

Gnomad4 SAS exome

AF:

0.733

Gnomad4 FIN exome

AF:

0.872

Gnomad4 NFE exome

AF:

0.830

Gnomad4 OTH exome

AF:

0.799

GnomAD4 genome

AF:

0.755

AC:

114778

AN:

152032

Hom.:

44359

Cov.:

AF XY:

0.758

AC XY:

56358

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.570

Gnomad4 AMR

AF:

0.802

Gnomad4 ASJ

AF:

0.792

Gnomad4 EAS

AF:

0.824

Gnomad4 SAS

AF:

0.722

Gnomad4 FIN

AF:

0.876

Gnomad4 NFE

AF:

0.832

Gnomad4 OTH

AF:

0.786

Alfa

AF:

0.812

Hom.:

41537

Bravo

AF:

0.742

TwinsUK

AF:

0.821

AC:

3045

ALSPAC

AF:

0.817

AC:

3149

ESP6500AA

AF:

0.677

AC:

2061

ESP6500EA

AF:

0.870

AC:

5295

ExAC

AF:

0.699

AC:

35526

Asia WGS

AF:

0.751

AC:

2612

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Platelet-type bleeding disorder 11

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.95

DANN

Benign

0.087

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00094

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-0.91

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.050

REVEL

Benign

0.028

Sift

Benign

1.0

Polyphen

0.0

Vest4

0.013

MutPred

0.18

Gain of disorder (P = 0.1036);

MPC

0.19

ClinPred

0.00014

GERP RS

-0.47

gMVP

0.013

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