19-55015005-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001083899.2(GP6):c.940C>G(p.Pro314Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,900 control chromosomes in the GnomAD database, including 19,636 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P314P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.48 ( 19636 hom., cov: 33)

Exomes 𝑓: 0.57 ( 241399 hom. )

Failed GnomAD Quality Control

Consequence

GP6
NM_001083899.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.277

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.248344E-5).

BP6

Variant 19-55015005-G-C is Benign according to our data. Variant chr19-55015005-G-C is described in ClinVar as [Benign]. Clinvar id is 257426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55015005-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_001083899.2 link	c.940C>G	p.Pro314Ala	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.940C>G	p.Pro314Ala	missense_variant	Exon 8 of 8	1	NM_001083899.2	ENSP00000308782.3		Q9HCN6-3
GP6	ENST00000417454.5 link	c.936C>G	p.Leu312Leu	synonymous_variant	Exon 8 of 8	1		ENSP00000394922.1		Q9HCN6-1

Frequencies

GnomAD3 genomes

AF:

0.482

AC:

73233

AN:

151784

Hom.:

19644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.547

Gnomad EAS

AF:

0.236

Gnomad SAS

AF:

0.438

Gnomad FIN

AF:

0.628

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.507

GnomAD2 exomes

AF:

0.520

AC:

126039

AN:

242548

AF XY:

0.525

show subpopulations

Gnomad AFR exome

AF:

0.245

Gnomad AMR exome

AF:

0.489

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.623

Gnomad NFE exome

AF:

0.602

Gnomad OTH exome

AF:

0.558

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.569

AC:

829184

AN:

1458520

Hom.:

241399

Cov.:

AF XY:

0.567

AC XY:

411367

AN XY:

725506

show subpopulations

Gnomad4 AFR exome

AF:

0.244

AC:

8129

AN:

33298

Gnomad4 AMR exome

AF:

0.496

AC:

22055

AN:

44466

Gnomad4 ASJ exome

AF:

0.539

AC:

14066

AN:

26084

Gnomad4 EAS exome

AF:

0.252

AC:

9963

AN:

39592

Gnomad4 SAS exome

AF:

0.463

AC:

39802

AN:

85980

Gnomad4 FIN exome

AF:

0.622

AC:

32973

AN:

52972

Gnomad4 NFE exome

AF:

0.600

AC:

666578

AN:

1110144

Gnomad4 Remaining exome

AF:

0.541

AC:

32614

AN:

60236

Heterozygous variant carriers

19275

38551

57826

77102

96377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

17822

35644

53466

71288

89110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.482

AC:

73245

AN:

151900

Hom.:

19636

Cov.:

AF XY:

0.483

AC XY:

35857

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.254

AC:

0.253936

AN:

0.253936

Gnomad4 AMR

AF:

0.531

AC:

0.530579

AN:

0.530579

Gnomad4 ASJ

AF:

0.547

AC:

0.546505

AN:

0.546505

Gnomad4 EAS

AF:

0.234

AC:

0.234145

AN:

0.234145

Gnomad4 SAS

AF:

0.438

AC:

0.437915

AN:

0.437915

Gnomad4 FIN

AF:

0.628

AC:

0.627553

AN:

0.627553

Gnomad4 NFE

AF:

0.604

AC:

0.604308

AN:

0.604308

Gnomad4 OTH

AF:

0.504

AC:

0.503788

AN:

0.503788

Heterozygous variant carriers

1810

3620

5430

7240

9050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.566

Hom.:

7576

Bravo

AF:

0.466

TwinsUK

AF:

0.599

AC:

2221

ALSPAC

AF:

0.596

AC:

2296

ESP6500AA

AF:

0.241

AC:

916

ESP6500EA

AF:

0.601

AC:

4939

ExAC

AF:

0.511

AC:

61627

Asia WGS

AF:

0.367

AC:

1278

AN:

3476

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GP6-related disorder

Benign:1

Oct 27, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

0.084

Eigen_PC

Benign

-0.063

FATHMM_MKL

Benign

0.54

MetaRNN

Benign

0.000052

MetaSVM

Benign

-1.2

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

REVEL

Benign

0.098

Sift

Benign

0.34

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.18

MPC

0.61

ClinPred

0.022

GERP RS

2.6

gMVP

0.041

Mutation Taster

=99/1

polymorphism (auto)

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