19-55014192-C-CGGGA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001083899.2(GP6):c.1752_1753insTCCC(p.Gly585SerfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 152,220 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00072 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: GP6 NM_001083899.2 frameshift
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.268

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 -16 ACMG points.

• BP6: Variant 19-55014192-C-CGGGA is Benign according to our data. Variant chr19-55014192-C-CGGGA is described in ClinVar as [Likely_benign]. Clinvar id is 777546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00592 (901/152220) while in subpopulation AFR AF= 0.0209 (870/41530). AF 95% confidence interval is 0.0198. There are 11 homozygotes in gnomad4. There are 435 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GP6	NM_001083899.2	c.1752_1753insTCCC	p.Gly585SerfsTer7	frameshift_variant	8/8	ENST00000310373.7
GP6-AS1	XR_001754012.3	n.121+7728_121+7729insGGGA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GP6	ENST00000310373.7	c.1752_1753insTCCC	p.Gly585SerfsTer7	frameshift_variant	8/8	1	NM_001083899.2
GP6-AS1	ENST00000593060.5	n.155+7728_155+7729insGGGA		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00594 AC: 903 AN: 152102 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00125 AC: 185 AN: 147996 Hom.: 1 AF XY: 0.000919 AC XY: 74 AN XY: 80484

Gnomad AFR exome AF: 0.0200

Gnomad AMR exome AF: 0.000872

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: 0.0000335

Gnomad OTH exome AF: 0.000228

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000722 AC: 413 AN: 571810 Hom.: 1 Cov.: 6 AF XY: 0.000543 AC XY: 168 AN XY: 309542

Gnomad4 AFR exome AF: 0.0191

Gnomad4 AMR exome AF: 0.00102

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: 0.0000421

Gnomad4 OTH exome AF: 0.00143

GnomAD4 genome AF: 0.00592 AC: 901 AN: 152220 Hom.: 11 Cov.: 32 AF XY: 0.00585 AC XY: 435 AN XY: 74420

Gnomad4 AFR AF: 0.0209

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00289 Hom.: 2

Bravo AF: 0.00646

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

GP6-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 18, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs761185718; hg19: chr19-55525560;