chr19-55015005-G-A

Variant names:

• chr19-55015005-G-A
• rs2304166
• NM_001083899.2:c.940C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001083899.2(GP6):​c.940C>T​(p.Pro314Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P314A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GP6 NM_001083899.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2688547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_001083899.2	c.940C>T	p.Pro314Ser	missense_variant	Exon 8 of 8	ENST00000310373.7	NP_001077368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7	c.940C>T	p.Pro314Ser	missense_variant	Exon 8 of 8	1	NM_001083899.2	ENSP00000308782.3
GP6	ENST00000417454.5	c.936C>T	p.Leu312Leu	synonymous_variant	Exon 8 of 8	1		ENSP00000394922.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1458722 Hom.: 0 Cov.: 46 AF XY: 0.00 AC XY: 0 AN XY: 725612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	1.0
Eigen	Benign	0.15
Eigen_PC	Benign	-0.0042
FATHMM_MKL	Benign	0.46	N
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.69	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.10
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.16
MutPred		0.24		Gain of phosphorylation at P314 (P = 0.0111);
MVP		0.67
MPC		0.64
ClinPred		0.74	D
GERP RS		2.6
gMVP		0.069

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: rs2304166; hg19: chr19-55526373;