rs201997410

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016363.5(GP6):c.881G>A(p.Arg294Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000278 in 1,606,416 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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. R294W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 2 hom. )

Consequence

GP6
NM_016363.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.109

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=0.0063310564).

BP6

Variant 19-55015060-C-T is Benign according to our data. Variant chr19-55015060-C-T is described in ClinVar as [Benign]. Clinvar id is 257425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00134 (204/152310) while in subpopulation AFR AF = 0.0046 (191/41564). AF 95% confidence interval is 0.00406. There are 0 homozygotes in GnomAd4. There are 94 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_001083899.2 link	c.885G>A	p.Pro295Pro	synonymous_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	ENST00000417454.5 link	c.881G>A	p.Arg294Gln	missense_variant	Exon 8 of 8	1		ENSP00000394922.1		Q9HCN6-1
GP6	ENST00000310373.7 link	c.885G>A	p.Pro295Pro	synonymous_variant	Exon 8 of 8	1	NM_001083899.2	ENSP00000308782.3		Q9HCN6-3

Frequencies

GnomAD3 genomes

AF:

0.00134

AC:

204

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00461

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000304

AC:

AN:

230558

AF XY:

0.000223

show subpopulations

Gnomad AFR exome

AF:

0.00469

Gnomad AMR exome

AF:

0.0000921

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000288

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000167

AC:

243

AN:

1454106

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

118

AN XY:

722768

show subpopulations

Gnomad4 AFR exome

AF:

0.00498

AC:

166

AN:

33304

Gnomad4 AMR exome

AF:

0.000254

AC:

AN:

43390

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25898

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39296

Gnomad4 SAS exome

AF:

0.0000589

AC:

AN:

84864

Gnomad4 FIN exome

AF:

0.0000190

AC:

AN:

52622

Gnomad4 NFE exome

AF:

0.0000397

AC:

AN:

1108914

Gnomad4 Remaining exome

AF:

0.000266

AC:

AN:

60060

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<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:

0.00134

AC:

204

AN:

152310

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00460

AC:

0.00459532

AN:

0.00459532

Gnomad4 AMR

AF:

0.000196

AC:

0.000196027

AN:

0.000196027

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000735

AC:

0.00007351

AN:

0.00007351

Gnomad4 OTH

AF:

0.00237

AC:

0.00236518

AN:

0.00236518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.000515

Hom.:

Bravo

AF:

0.00182

ESP6500AA

AF:

0.00307

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000397

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 31, 2024

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.28

M_CAP

Benign

0.0033

MetaRNN

Benign

0.0063

T;T

MetaSVM

Benign

-0.83

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.070

Sift

Benign

0.20

T;T

Sift4G

Benign

0.35

T;T

Polyphen

1.0

D;D

Vest4

0.12

MVP

0.64

ClinPred

0.026

GERP RS

0.89

Varity_R

0.087

Mutation Taster

=98/2

polymorphism

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