2-46616943-A-AG

Variant names:

• chr2-46616943-A-AG
• rs5830913
• NM_002643.4:c.-22+26_-22+27insC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002643.4(PIGF):​c.-22+26_-22+27insC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (76168 hom., cov: 0)
  • Exomes 𝑓: 1.0 (158725 hom.)
• Consequence: PIGF NM_002643.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.20
• Publications: 1 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]

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]

CRIPT Gene-Disease associations (from GenCC):

• Rothmund-Thomson syndrome type 3

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 2-46616943-A-AG is Benign according to our data. Variant chr2-46616943-A-AG is described in ClinVar as Benign. ClinVar VariationId is 1250607.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002643.4. 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
	PIGF	NM_002643.4	MANE Select	c.-22+26_-22+27insC		intron	N/A	NP_002634.1	Q6IB04
	PIGF	NM_173074.3		c.-22+26_-22+27insC		intron	N/A	NP_775097.1	Q07326-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGF	ENST00000281382.11	TSL:1 MANE Select	c.-22+26_-22+27insC		intron	N/A	ENSP00000281382.6	Q07326-1
	PIGF	ENST00000306465.8	TSL:1	c.-22+26_-22+27insC		intron	N/A	ENSP00000302663.4	Q07326-2
	PIGF	ENST00000903158.1		c.-375_-374insC		5_prime_UTR	Exon 1 of 6	ENSP00000573217.1

Frequencies

GnomAD3 genomes AF: 1.00 AC: 152224 AN: 152230 Hom.: 76109 Cov.: 0

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD4 exome AF: 1.00 AC: 317459 AN: 317468 Hom.: 158725 Cov.: 0 AF XY: 1.00 AC XY: 167998 AN XY: 168004

African (AFR) AF: 1.00 AC: 8076 AN: 8076

American (AMR) AF: 1.00 AC: 10694 AN: 10694

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 9490 AN: 9490

East Asian (EAS) AF: 1.00 AC: 17690 AN: 17690

South Asian (SAS) AF: 1.00 AC: 40868 AN: 40868

European-Finnish (FIN) AF: 1.00 AC: 20096 AN: 20096

Middle Eastern (MID) AF: 1.00 AC: 1412 AN: 1412

European-Non Finnish (NFE) AF: 1.00 AC: 190678 AN: 190686

Other (OTH) AF: 1.00 AC: 18455 AN: 18456

GnomAD4 genome AF: 1.00 AC: 152342 AN: 152348 Hom.: 76168 Cov.: 0 AF XY: 1.00 AC XY: 74479 AN XY: 74482

African (AFR) AF: 1.00 AC: 41590 AN: 41590

American (AMR) AF: 1.00 AC: 15310 AN: 15310

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3470 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5156 AN: 5156

South Asian (SAS) AF: 1.00 AC: 4833 AN: 4834

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10626

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68037 AN: 68042

Other (OTH) AF: 1.00 AC: 2114 AN: 2114

Alfa AF: 1.00 Hom.: 8165

Bravo AF: 1.00

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs5830913; hg19: chr2-46844082;