rs754459187

Variant names:

• chr19-55014278-GTTTTT-G
• rs754459187
• ENST00000310373.7:c.1662_1666delAAAAA

Your query was ambiguous. Multiple possible variants found:

• chr19-55014278-GTTTTT-G
• chr19-55014278-GTTTTT-GTTTT
• chr19-55014278-GTTTTT-GTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001083899.2(GP6):​c.1662_1666delAAAAA​(p.Lys554AsnfsTer35) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000423 in 1,181,148 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: GP6 NM_001083899.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083899.2. 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.*638_*642delAAAAA		3_prime_UTR	Exon 8 of 8	NP_057447.5	Q9HCN6-1
	GP6	NM_001083899.2		c.1662_1666delAAAAA	p.Lys554AsnfsTer35	frameshift	Exon 8 of 8	NP_001077368.2	Q9HCN6-3
	GP6	NM_001256017.2		c.*638_*642delAAAAA		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.1662_1666delAAAAA	p.Lys554AsnfsTer35	frameshift	Exon 8 of 8	ENSP00000308782.3	Q9HCN6-3
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.*638_*642delAAAAA		3_prime_UTR	Exon 8 of 8	ENSP00000394922.1	Q9HCN6-1
	GP6	ENST00000333884.2	TSL:1	c.*638_*642delAAAAA		3_prime_UTR	Exon 7 of 7	ENSP00000334552.2	Q9HCN6-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000422 AC: 1 AN: 236850 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000923

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000423 AC: 5 AN: 1181148 Hom.: 0 AF XY: 0.00000166 AC XY: 1 AN XY: 600824

African (AFR) AF: 0.00 AC: 0 AN: 28160

American (AMR) AF: 0.00 AC: 0 AN: 44354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24394

East Asian (EAS) AF: 0.00 AC: 0 AN: 38388

South Asian (SAS) AF: 0.00 AC: 0 AN: 80670

European-Finnish (FIN) AF: 0.0000875 AC: 4 AN: 45716

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5234

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 862818

Other (OTH) AF: 0.0000194 AC: 1 AN: 51414

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs754459187; hg19: chr19-55525646;