19-55014140-G-A

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.1805C>T(p.Thr602Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 694,732 control chromosomes in the GnomAD database, including 1,157 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. T602T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.057 ( 817 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 340 hom. )

Consequence

GP6
NM_001083899.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.642

Publications

6 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=0.00459826).

BP6

Variant 19-55014140-G-A is Benign according to our data. Variant chr19-55014140-G-A is described in ClinVar as Benign. ClinVar VariationId is 257415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083899.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GP6	NM_016363.5	MANE Select	c.*781C>T		3_prime_UTR	Exon 8 of 8	NP_057447.5	Q9HCN6-1
GP6	NM_001083899.2		c.1805C>T	p.Thr602Met	missense	Exon 8 of 8	NP_001077368.2	Q9HCN6-3
GP6	NM_001256017.2		c.*781C>T		3_prime_UTR	Exon 7 of 7	NP_001242946.2	Q9HCN6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GP6	ENST00000310373.7	TSL:1	c.1805C>T	p.Thr602Met	missense	Exon 8 of 8	ENSP00000308782.3	Q9HCN6-3
GP6	ENST00000417454.5	TSL:1 MANE Select	c.*781C>T		3_prime_UTR	Exon 8 of 8	ENSP00000394922.1	Q9HCN6-1
GP6	ENST00000333884.2	TSL:1	c.*781C>T		3_prime_UTR	Exon 7 of 7	ENSP00000334552.2	Q9HCN6-2

Frequencies

GnomAD3 genomes

AF:

0.0565

AC:

8589

AN:

152016

Hom.:

814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0237

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.0439

GnomAD2 exomes

AF:

0.0128

AC:

1679

AN:

130840

AF XY:

0.0105

show subpopulations

Gnomad AFR exome

AF:

0.207

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.000123

Gnomad EAS exome

AF:

0.0000947

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000753

Gnomad OTH exome

AF:

0.00814

GnomAD4 exome

AF:

0.00808

AC:

4385

AN:

542598

Hom.:

340

Cov.:

AF XY:

0.00646

AC XY:

1898

AN XY:

293962

show subpopulations

African (AFR)

AF:

0.200

AC:

3136

AN:

15710

American (AMR)

AF:

0.0131

AC:

450

AN:

34470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19866

East Asian (EAS)

AF:

0.00

AC:

AN:

31548

South Asian (SAS)

AF:

0.000904

AC:

AN:

61942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32734

Middle Eastern (MID)

AF:

0.0105

AC:

AN:

3990

European-Non Finnish (NFE)

AF:

0.000567

AC:

177

AN:

312160

Other (OTH)

AF:

0.0174

AC:

524

AN:

30178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

242

484

725

967

1209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.0567

AC:

8619

AN:

152134

Hom.:

817

Cov.:

AF XY:

0.0550

AC XY:

4088

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.195

AC:

8099

AN:

41452

American (AMR)

AF:

0.0236

AC:

361

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00124

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68016

Other (OTH)

AF:

0.0435

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

353

706

1060

1413

1766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0147

Hom.:

389

Bravo

AF:

0.0661

ESP6500AA

AF:

0.143

AC:

480

ESP6500EA

AF:

0.00164

AC:

ExAC

AF:

0.00820

AC:

688

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0086

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.1

PhyloP100

-0.64

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.080

REVEL

Benign

0.021

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.82

Vest4

0.21

MPC

0.63

ClinPred

0.026

GERP RS

-0.47

gMVP

0.085

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over