rs2298784

Variant names:

• chr18-62109920-T-C
• rs2298784
• NM_176787.5:c.1488A>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_176787.5(PIGN):​c.1488A>G​(p.Ala496Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0061 in 1,613,146 control chromosomes in the GnomAD database, including 283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0097 (45 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (238 hom.)
• Consequence: PIGN NM_176787.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0200

Genes affected

PIGN (HGNC:8967): (phosphatidylinositol glycan anchor biosynthesis class N) This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is expressed in the endoplasmic reticulum and transfers phosphoethanolamine (EtNP) to the first mannose of the GPI anchor. Two alternatively spliced variants, which encode an identical isoform, have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 18-62109920-T-C is Benign according to our data. Variant chr18-62109920-T-C is described in ClinVar as [Benign]. Clinvar id is 472211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGN	NM_176787.5	c.1488A>G	p.Ala496Ala	synonymous_variant	Exon 17 of 31	ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000640252.2	c.1488A>G	p.Ala496Ala	synonymous_variant	Exon 17 of 31	1	NM_176787.5	ENSP00000492233.1
PIGN	ENST00000400334.7	c.1488A>G	p.Ala496Ala	synonymous_variant	Exon 16 of 30	1		ENSP00000383188.2
PIGN	ENST00000638424.1	n.1488A>G		non_coding_transcript_exon_variant	Exon 15 of 29	5		ENSP00000491963.1

Frequencies

GnomAD3 genomes AF: 0.00967 AC: 1470 AN: 151972 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.00288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.0689

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00281

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.0125 AC: 3110 AN: 248676 Hom.: 93 AF XY: 0.0124 AC XY: 1669 AN XY: 134884

Gnomad AFR exome AF: 0.00252

Gnomad AMR exome AF: 0.000522

Gnomad ASJ exome AF: 0.00378

Gnomad EAS exome AF: 0.0628

Gnomad SAS exome AF: 0.00248

Gnomad FIN exome AF: 0.0654

Gnomad NFE exome AF: 0.00289

Gnomad OTH exome AF: 0.0131

GnomAD4 exome AF: 0.00573 AC: 8369 AN: 1461056 Hom.: 238 Cov.: 30 AF XY: 0.00563 AC XY: 4094 AN XY: 726808

Gnomad4 AFR exome AF: 0.00221

Gnomad4 AMR exome AF: 0.000627

Gnomad4 ASJ exome AF: 0.00429

Gnomad4 EAS exome AF: 0.0719

Gnomad4 SAS exome AF: 0.00274

Gnomad4 FIN exome AF: 0.0629

Gnomad4 NFE exome AF: 0.00113

Gnomad4 OTH exome AF: 0.00738

GnomAD4 genome AF: 0.00966 AC: 1469 AN: 152090 Hom.: 45 Cov.: 32 AF XY: 0.0131 AC XY: 971 AN XY: 74354

Gnomad4 AFR AF: 0.00287

Gnomad4 AMR AF: 0.000786

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.0688

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.00281

Gnomad4 OTH AF: 0.00711

Alfa AF: 0.00239 Hom.: 4

Bravo AF: 0.00435

Asia WGS AF: 0.0330 AC: 114 AN: 3478

EpiCase AF: 0.000982

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Sep 18, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Aug 19, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Multiple congenital anomalies-hypotonia-seizures syndrome 1 Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.1
DANN	Benign	0.75

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: rs2298784; hg19: chr18-59777153; COSMIC: COSV62949472; COSMIC: COSV62949472;