chr2-46617108-G-A

Variant names:

• chr2-46617108-G-A
• rs113423551
• ENST00000486447.1:n.608+85G>A

Variant summary

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

The ENST00000486447.1(CRIPT):​n.608+85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 692,158 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: CRIPT ENST00000486447.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 6 publications found

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]

PIGF Gene-Disease associations (from GenCC):

• onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGF	NM_002643.4	c.-160C>T		upstream_gene_variant		ENST00000281382.11	NP_002634.1
CRIPT	NM_014171.6	c.-175G>A		upstream_gene_variant		ENST00000238892.4	NP_054890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGF	ENST00000281382.11	c.-160C>T		upstream_gene_variant		1	NM_002643.4	ENSP00000281382.6
CRIPT	ENST00000238892.4	c.-175G>A		upstream_gene_variant		1	NM_014171.6	ENSP00000238892.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000289 AC: 2 AN: 692158 Hom.: 0 Cov.: 9 AF XY: 0.00000551 AC XY: 2 AN XY: 362800

African (AFR) AF: 0.00 AC: 0 AN: 18386

American (AMR) AF: 0.00 AC: 0 AN: 33350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19466

East Asian (EAS) AF: 0.00 AC: 0 AN: 32532

South Asian (SAS) AF: 0.00 AC: 0 AN: 62068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2720

European-Non Finnish (NFE) AF: 0.00000440 AC: 2 AN: 454544

Other (OTH) AF: 0.00 AC: 0 AN: 35016

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 283

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.95
PhyloP100		-0.069
PromoterAI		0.079	Neutral

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: rs113423551; hg19: chr2-46844247;