Variant 19-55014086-ATCAGGGTAATTGACATAT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP3BS1_Supporting

The NM_001083899.2(GP6):c.1841_1858delATATGTCAATTACCCTGA(p.Asn614_Leu619del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000398 in 653,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00040 ( 0 hom. )

Consequence

GP6
NM_001083899.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.347

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_001083899.2

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000387 (59/152266) while in subpopulation NFE AF= 0.000764 (52/68020). AF 95% confidence interval is 0.000599. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GP6	NM_001083899.2 link	c.1841_1858delATATGTCAATTACCCTGA	p.Asn614_Leu619del	disruptive_inframe_deletion	8/8	ENST00000310373.7	NP_001077368.2	Q9HCN6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7 link	c.1841_1858delATATGTCAATTACCCTGA	p.Asn614_Leu619del	disruptive_inframe_deletion	8/8	1	NM_001083899.2	ENSP00000308782.3		Q9HCN6-3
GP6	ENST00000417454 link	c.817_834delATATGTCAATTACCCTGA		3_prime_UTR_variant	8/8	1		ENSP00000394922.1		Q9HCN6-1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000764

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000232

AC:

AN:

129264

Hom.:

AF XY:

0.000270

AC XY:

AN XY:

70480

show subpopulations

Gnomad AFR exome

AF:

0.000161

Gnomad AMR exome

AF:

0.000164

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000497

Gnomad OTH exome

AF:

0.000249

GnomAD4 exome

AF:

0.000401

AC:

201

AN:

501468

Hom.:

AF XY:

0.000367

AC XY:

100

AN XY:

272488

show subpopulations

Gnomad4 AFR exome

AF:

0.000134

Gnomad4 AMR exome

AF:

0.000212

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000597

Gnomad4 OTH exome

AF:

0.000760

GnomAD4 genome

AF:

0.000387

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000764

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.000408

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 27, 2022

This variant, c.1841_1858del, results in the deletion of 6 amino acid(s) of the GP6 protein (p.Asn614_Leu619del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs774618165, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with GP6-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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