ENST00000310373.7:c.1206_1209dupTCTG

Variant names:

• chr19-55014735-G-GCAGA
• rs768134535
• ENST00000310373.7:c.1206_1209dupTCTG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000310373.7(GP6):​c.1206_1209dupTCTG​(p.Pro404SerfsTer61) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 1,613,468 control chromosomes in the GnomAD database, including 1,636 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L403L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.047 (291 hom., cov: 31)
  • Exomes 𝑓: 0.031 (1345 hom.)
• Consequence: GP6 ENST00000310373.7 frameshift
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.173
• Publications: 5 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 -16 ACMG points.

• BP6: Variant 19-55014735-G-GCAGA is Benign according to our data. Variant chr19-55014735-G-GCAGA is described in ClinVar as Benign. ClinVar VariationId is 257410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000310373.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	NM_016363.5	MANE Select	c.*182_*185dupTCTG		3_prime_UTR	Exon 8 of 8	NP_057447.5	Q9HCN6-1
	GP6	NM_001083899.2		c.1206_1209dupTCTG	p.Pro404SerfsTer61	frameshift	Exon 8 of 8	NP_001077368.2	Q9HCN6-3
	GP6	NM_001256017.2		c.*182_*185dupTCTG		3_prime_UTR	Exon 7 of 7	NP_001242946.2	Q9HCN6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	ENST00000310373.7	TSL:1	c.1206_1209dupTCTG	p.Pro404SerfsTer61	frameshift	Exon 8 of 8	ENSP00000308782.3	Q9HCN6-3
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.*182_*185dupTCTG		3_prime_UTR	Exon 8 of 8	ENSP00000394922.1	Q9HCN6-1
	GP6	ENST00000333884.2	TSL:1	c.*182_*185dupTCTG		3_prime_UTR	Exon 7 of 7	ENSP00000334552.2	Q9HCN6-2

Frequencies

GnomAD3 genomes AF: 0.0469 AC: 7123 AN: 151980 Hom.: 291 Cov.: 31

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0350

GnomAD2 exomes AF: 0.0467 AC: 11550 AN: 247204 AF XY: 0.0439

Gnomad AFR exome AF: 0.0784

Gnomad AMR exome AF: 0.0907

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.145

Gnomad FIN exome AF: 0.0142

Gnomad NFE exome AF: 0.0197

Gnomad OTH exome AF: 0.0327

GnomAD4 exome AF: 0.0308 AC: 44944 AN: 1461370 Hom.: 1345 Cov.: 39 AF XY: 0.0309 AC XY: 22465 AN XY: 726974

African (AFR) AF: 0.0816 AC: 2731 AN: 33468

American (AMR) AF: 0.0892 AC: 3982 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.0117 AC: 305 AN: 26042

East Asian (EAS) AF: 0.172 AC: 6801 AN: 39650

South Asian (SAS) AF: 0.0585 AC: 5037 AN: 86162

European-Finnish (FIN) AF: 0.0138 AC: 737 AN: 53410

Middle Eastern (MID) AF: 0.0121 AC: 70 AN: 5768

European-Non Finnish (NFE) AF: 0.0208 AC: 23169 AN: 1111856

Other (OTH) AF: 0.0350 AC: 2112 AN: 60380

GnomAD4 genome AF: 0.0469 AC: 7137 AN: 152098 Hom.: 291 Cov.: 31 AF XY: 0.0474 AC XY: 3526 AN XY: 74356

African (AFR) AF: 0.0783 AC: 3249 AN: 41480

American (AMR) AF: 0.0787 AC: 1201 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3470

East Asian (EAS) AF: 0.148 AC: 762 AN: 5138

South Asian (SAS) AF: 0.0649 AC: 313 AN: 4822

European-Finnish (FIN) AF: 0.0155 AC: 165 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0194 AC: 1319 AN: 67990

Other (OTH) AF: 0.0374 AC: 79 AN: 2110

Alfa AF: 0.00939 Hom.: 2

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17
Mutation Taster		=165/35	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs768134535; hg19: chr19-55526103; COSMIC: COSV59979980;