2-46617080-C-CG

Position:

• chr2-46617080-C-CG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000486447.1(CRIPT):​n.608+58dup variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (75831 hom., cov: 0)
  • Exomes 𝑓: 1.0 (275335 hom.)
• Consequence: CRIPT ENST00000486447.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0240

Genes affected

CRIPT (HGNC:14312): (CXXC repeat containing interactor of PDZ3 domain) This gene encodes a protein that binds to the PDZ3 peptide recognition domain. The encoded protein may modulates protein interactions with the cytoskeleton. A mutation in this gene resulted in short stature with microcephaly and distinctive facies. [provided by RefSeq, Jun 2014]

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-46617080-C-CG is Benign according to our data. Variant chr2-46617080-C-CG is described in ClinVar as [Benign]. Clinvar id is 1240553.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGF	NM_002643.4			upstream_gene_variant		ENST00000281382.11	NP_002634.1
PIGF	NM_173074.3			upstream_gene_variant			NP_775097.1
PIGF	XM_005264369.4			upstream_gene_variant			XP_005264426.1
PIGF	XM_011532908.4			upstream_gene_variant			XP_011531210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGF	ENST00000281382.11			upstream_gene_variant		1	NM_002643.4	ENSP00000281382	P1

Frequencies

GnomAD3 genomes AF: 0.998 AC: 151878 AN: 152214 Hom.: 75772 Cov.: 0

Gnomad AFR AF: 0.999

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.998

Gnomad ASJ AF: 0.994

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 0.994

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.999

GnomAD4 exome AF: 0.998 AC: 551895 AN: 553122 Hom.: 275335 Cov.: 7 AF XY: 0.998 AC XY: 292265 AN XY: 292910

Gnomad4 AFR exome AF: 0.999

Gnomad4 AMR exome AF: 0.999

Gnomad4 ASJ exome AF: 0.994

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.993

Gnomad4 NFE exome AF: 0.998

Gnomad4 OTH exome AF: 0.998

GnomAD4 genome AF: 0.998 AC: 151996 AN: 152332 Hom.: 75831 Cov.: 0 AF XY: 0.998 AC XY: 74308 AN XY: 74480

Gnomad4 AFR AF: 0.999

Gnomad4 AMR AF: 0.998

Gnomad4 ASJ AF: 0.994

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 0.994

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.999

Alfa AF: 0.999 Hom.: 8128

Bravo AF: 0.998

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs5830914; hg19: chr2-46844219;