rs2304167

Variant names:

• chr19-55015713-C-T
• rs2304167
• NM_016363.5:c.745G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016363.5(GP6):​c.745G>A​(p.Ala249Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,565,964 control chromosomes in the GnomAD database, including 508,174 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 0.74 (43220 hom., cov: 30)
  • Exomes 𝑓: 0.81 (464954 hom.)
• Consequence: GP6 NM_016363.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.77
• Publications: 49 publications found

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-AS1 (HGNC:55305): (GP6 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.0152187E-6).
• BP6: Variant 19-55015713-C-T is Benign according to our data. Variant chr19-55015713-C-T is described in ClinVar as Benign. ClinVar VariationId is 257424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016363.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	NM_016363.5	MANE Select	c.745G>A	p.Ala249Thr	missense	Exon 7 of 8	NP_057447.5
	GP6	NM_001083899.2		c.745G>A	p.Ala249Thr	missense	Exon 7 of 8	NP_001077368.2
	GP6	NM_001256017.2		c.691G>A	p.Ala231Thr	missense	Exon 6 of 7	NP_001242946.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.745G>A	p.Ala249Thr	missense	Exon 7 of 8	ENSP00000394922.1
	GP6	ENST00000310373.7	TSL:1	c.745G>A	p.Ala249Thr	missense	Exon 7 of 8	ENSP00000308782.3
	GP6	ENST00000333884.2	TSL:1	c.691G>A	p.Ala231Thr	missense	Exon 6 of 7	ENSP00000334552.2

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112611 AN: 151798 Hom.: 43216 Cov.: 30

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.783

GnomAD2 exomes AF: 0.797 AC: 198230 AN: 248688 AF XY: 0.797

Gnomad AFR exome AF: 0.506

Gnomad AMR exome AF: 0.830

Gnomad ASJ exome AF: 0.797

Gnomad EAS exome AF: 0.835

Gnomad FIN exome AF: 0.871

Gnomad NFE exome AF: 0.825

Gnomad OTH exome AF: 0.810

GnomAD4 exome AF: 0.808 AC: 1143233 AN: 1414048 Hom.: 464954 Cov.: 27 AF XY: 0.808 AC XY: 571058 AN XY: 706660

African (AFR) AF: 0.509 AC: 16637 AN: 32714

American (AMR) AF: 0.825 AC: 36817 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 20510 AN: 25814

East Asian (EAS) AF: 0.806 AC: 31822 AN: 39458

South Asian (SAS) AF: 0.731 AC: 62320 AN: 85240

European-Finnish (FIN) AF: 0.871 AC: 46496 AN: 53386

Middle Eastern (MID) AF: 0.782 AC: 4452 AN: 5692

European-Non Finnish (NFE) AF: 0.821 AC: 877401 AN: 1068330

Other (OTH) AF: 0.796 AC: 46778 AN: 58790

GnomAD4 genome AF: 0.742 AC: 112658 AN: 151916 Hom.: 43220 Cov.: 30 AF XY: 0.745 AC XY: 55329 AN XY: 74266

African (AFR) AF: 0.522 AC: 21591 AN: 41338

American (AMR) AF: 0.799 AC: 12191 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2749 AN: 3472

East Asian (EAS) AF: 0.821 AC: 4232 AN: 5154

South Asian (SAS) AF: 0.721 AC: 3475 AN: 4818

European-Finnish (FIN) AF: 0.876 AC: 9277 AN: 10594

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56548 AN: 67970

Other (OTH) AF: 0.781 AC: 1646 AN: 2108

Alfa AF: 0.793 Hom.: 131588

Bravo AF: 0.727

TwinsUK AF: 0.821 AC: 3043

ALSPAC AF: 0.817 AC: 3147

ESP6500AA AF: 0.524 AC: 2097

ESP6500EA AF: 0.830 AC: 6939

ExAC AF: 0.788 AC: 95263

Asia WGS AF: 0.748 AC: 2601 AN: 3478

EpiCase AF: 0.824

EpiControl AF: 0.827

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.57
DANN	Benign	0.64
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.012	N
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.90	L
PhyloP100		-2.8
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.011
Sift	Benign	0.98	T
Sift4G	Benign	0.40	T
Polyphen		0.0010	B
Vest4		0.015
MPC		0.19
ClinPred		0.0048	T
GERP RS		-6.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.15
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs2304167; hg19: chr19-55527081; COSMIC: COSV59979310;