chr19-55014140-G-A

Position:

• chr19-55014140-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (817 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (340 hom.)
• Consequence: GP6 NM_001083899.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.642

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GP6	NM_001083899.2	c.1805C>T	p.Thr602Met	missense_variant	8/8	ENST00000310373.7	NP_001077368.2
GP6-AS1	XR_001754012.3	n.121+7676G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7	c.1805C>T	p.Thr602Met	missense_variant	8/8	1	NM_001083899.2	ENSP00000308782
GP6-AS1	ENST00000593060.5	n.155+7676G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0565 AC: 8589 AN: 152016 Hom.: 814 Cov.: 32

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

GnomAD3 exomes AF: 0.0128 AC: 1679 AN: 130840 Hom.: 147 AF XY: 0.0105 AC XY: 746 AN XY: 71184

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 SAS exome AF: 0.000798

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.: 3 AF XY: 0.00646 AC XY: 1898 AN XY: 293962

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.0131

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000904

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000567

Gnomad4 OTH exome AF: 0.0174

GnomAD4 genome AF: 0.0567 AC: 8619 AN: 152134 Hom.: 817 Cov.: 32 AF XY: 0.0550 AC XY: 4088 AN XY: 74370

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.0236

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000823

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.00352 Hom.: 53

Bravo AF: 0.0661

ESP6500AA AF: 0.143 AC: 480

ESP6500EA AF: 0.00164 AC: 11

ExAC AF: 0.00820 AC: 688

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Uncertain	0.99
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0086	N
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.021
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.82	P
Vest4		0.21
MPC		0.63
ClinPred		0.026	T
GERP RS		-0.47
gMVP		0.085

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

Other links and lift over

dbSNP: rs2886416; hg19: chr19-55525508;