2-46581484-G-A

Variant names:

• chr2-46581484-G-A
• rs746839063
• NM_002643.4:c.654C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002643.4(PIGF):​c.654C>T​(p.Asn218Asn) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIGF NM_002643.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.95
• Publications: 0 publications found

Genes affected

PIGF (HGNC:8962): (phosphatidylinositol glycan anchor biosynthesis class F) This gene encodes a protein involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor, a glycolipid containing three mannose molecules in its core backbone, is found on many blood cells where it serves to anchor proteins to the cell surface. The encoded protein and another GPI synthesis protein, PIGO, function in the transfer of ethanolaminephosphate to the third mannose in GPI. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

RHOQ (HGNC:17736): (ras homolog family member Q) This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. The encoded protein is an important signalling protein for sarcomere assembly and has been shown to play a significant role in the exocytosis of the solute carrier family 2, facilitated glucose transporter member 4 and other proteins, possibly acting as the signal that turns on the membrane fusion machinery. Three related pseudogene have been identified on chromosomes 2 and 14. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGF	NM_002643.4	c.654C>T	p.Asn218Asn	synonymous_variant	Exon 6 of 6	ENST00000281382.11	NP_002634.1
RHOQ	NM_012249.4	c.*401G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000238738.9	NP_036381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGF	ENST00000281382.11	c.654C>T	p.Asn218Asn	synonymous_variant	Exon 6 of 6	1	NM_002643.4	ENSP00000281382.6
RHOQ	ENST00000238738.9	c.*401G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_012249.4	ENSP00000238738.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000424 AC: 1 AN: 236050 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: 0.00

Gnomad OTH exome AF: 0.000172

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		3.9
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs746839063; hg19: chr2-46808623;