19-55014977-T-G

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.968A>C(p.Lys323Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 1,612,488 control chromosomes in the GnomAD database, including 571,648 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K323S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.82 ( 50959 hom., cov: 33)

Exomes 𝑓: 0.84 ( 520689 hom. )

Consequence

GP6
NM_001083899.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.191

Publications

73 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=1.233405E-6).

BP6

Variant 19-55014977-T-G is Benign according to our data. Variant chr19-55014977-T-G is described in ClinVar as Benign. ClinVar VariationId is 257428.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_001083899.2 link	c.968A>C	p.Lys323Thr	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.968A>C	p.Lys323Thr	missense_variant	Exon 8 of 8	1	NM_001083899.2	ENSP00000308782.3		Q9HCN6-3
GP6	ENST00000417454.5 link	c.964A>C	p.Asn322His	missense_variant	Exon 8 of 8	1		ENSP00000394922.1		Q9HCN6-1

Frequencies

GnomAD3 genomes

AF:

0.815

AC:

123699

AN:

151706

Hom.:

50937

Cov.:

show subpopulations

Gnomad AFR

AF:

0.695

Gnomad AMI

AF:

0.768

Gnomad AMR

AF:

0.887

Gnomad ASJ

AF:

0.805

Gnomad EAS

AF:

0.976

Gnomad SAS

AF:

0.787

Gnomad FIN

AF:

0.891

Gnomad MID

AF:

0.846

Gnomad NFE

AF:

0.851

Gnomad OTH

AF:

0.836

GnomAD2 exomes

AF:

0.851

AC:

209926

AN:

246550

AF XY:

0.847

show subpopulations

Gnomad AFR exome

AF:

0.683

Gnomad AMR exome

AF:

0.927

Gnomad ASJ exome

AF:

0.811

Gnomad EAS exome

AF:

0.984

Gnomad FIN exome

AF:

0.884

Gnomad NFE exome

AF:

0.845

Gnomad OTH exome

AF:

0.845

GnomAD4 exome

AF:

0.843

AC:

1231770

AN:

1460662

Hom.:

520689

Cov.:

AF XY:

0.842

AC XY:

612082

AN XY:

726582

show subpopulations

African (AFR)

AF:

0.686

AC:

22947

AN:

33452

American (AMR)

AF:

0.922

AC:

41177

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.807

AC:

21086

AN:

26128

East Asian (EAS)

AF:

0.982

AC:

38951

AN:

39682

South Asian (SAS)

AF:

0.792

AC:

68205

AN:

86168

European-Finnish (FIN)

AF:

0.885

AC:

46954

AN:

53066

Middle Eastern (MID)

AF:

0.799

AC:

4610

AN:

5768

European-Non Finnish (NFE)

AF:

0.843

AC:

937188

AN:

1111366

Other (OTH)

AF:

0.839

AC:

50652

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

10333

20666

31000

41333

51666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21102

42204

63306

84408

105510

<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:

0.815

AC:

123778

AN:

151826

Hom.:

50959

Cov.:

AF XY:

0.819

AC XY:

60757

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.695

AC:

28757

AN:

41392

American (AMR)

AF:

0.888

AC:

13550

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.805

AC:

2793

AN:

3468

East Asian (EAS)

AF:

0.975

AC:

5035

AN:

5162

South Asian (SAS)

AF:

0.787

AC:

3797

AN:

4824

European-Finnish (FIN)

AF:

0.891

AC:

9398

AN:

10552

Middle Eastern (MID)

AF:

0.845

AC:

245

AN:

290

European-Non Finnish (NFE)

AF:

0.851

AC:

57744

AN:

67856

Other (OTH)

AF:

0.836

AC:

1763

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1139

2279

3418

4558

5697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<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:

0.838

Hom.:

183722

Bravo

AF:

0.810

TwinsUK

AF:

0.846

AC:

3138

ALSPAC

AF:

0.843

AC:

3250

ESP6500AA

AF:

0.690

AC:

2707

ESP6500EA

AF:

0.849

AC:

7026

ExAC

AF:

0.842

AC:

101730

Asia WGS

AF:

0.882

AC:

3064

AN:

3476

EpiCase

AF:

0.843

EpiControl

AF:

0.841

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

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

0.052

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.0

(source)

DANN

Benign

0.37

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0011

MetaRNN

Benign

0.0000012

MetaSVM

Benign

-0.92

PhyloP100

0.19

PrimateAI

Benign

0.35

PROVEAN

Benign

0.53

REVEL

Benign

0.030

Sift

Benign

1.0

Sift4G

Benign

0.75

Polyphen

0.0

Vest4

0.056

MPC

0.19

ClinPred

0.0023

GERP RS

2.6

Varity_R

0.032

gMVP

0.032

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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