rs1613662

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_016363.5(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. 15/21 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_016363.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.373

Publications

122 publications found

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=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 VariationId is 257422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_016363.5 link	c.655C>T	p.Pro219Ser	missense_variant	Exon 5 of 8	ENST00000417454.5	NP_057447.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000417454.5 link	c.655C>T	p.Pro219Ser	missense_variant	Exon 5 of 8	1	NM_016363.5	ENSP00000394922.1

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

GnomAD2 exomes

AF:

0.854

AC:

133645

AN:

156582

AF XY:

0.848

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 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

African (AFR)

AF:

0.764

AC:

23993

AN:

31386

American (AMR)

AF:

0.918

AC:

32823

AN:

35768

Ashkenazi Jewish (ASJ)

AF:

0.794

AC:

19919

AN:

25092

East Asian (EAS)

AF:

0.981

AC:

35039

AN:

35724

South Asian (SAS)

AF:

0.790

AC:

62447

AN:

79050

European-Finnish (FIN)

AF:

0.884

AC:

43679

AN:

49418

Middle Eastern (MID)

AF:

0.802

AC:

4495

AN:

5602

European-Non Finnish (NFE)

AF:

0.838

AC:

896390

AN:

1069424

Other (OTH)

AF:

0.840

AC:

48504

AN:

57740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

8784

17567

26351

35134

43918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20454

40908

61362

81816

102270

<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:

0.834

AC:

126955

AN:

152170

Hom.:

53189

Cov.:

AF XY:

0.839

AC XY:

62391

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.773

AC:

32084

AN:

41480

American (AMR)

AF:

0.887

AC:

13552

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.795

AC:

2761

AN:

3472

East Asian (EAS)

AF:

0.976

AC:

5062

AN:

5188

South Asian (SAS)

AF:

0.786

AC:

3789

AN:

4820

European-Finnish (FIN)

AF:

0.890

AC:

9444

AN:

10610

Middle Eastern (MID)

AF:

0.850

AC:

250

AN:

294

European-Non Finnish (NFE)

AF:

0.846

AC:

57532

AN:

68018

Other (OTH)

AF:

0.845

AC:

1782

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1058

2116

3173

4231

5289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

888

1776

2664

3552

4440

<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:

0.839

Hom.:

242917

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

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

This variant is associated with the following publications: (PMID: 31699788, 11571236, 22133274, 19786296, 25525159, 20227257, 21232005, 20723028, 18349091, 19278955) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

-0.37

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over