2-196842521-G-GA

Position:

• chr2-196842521-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_024989.4(PGAP1):​c.2630+199_2630+200insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 148,976 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.015 (24 hom., cov: 32)
• Consequence: PGAP1 NM_024989.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.664

Genes affected

PGAP1 (HGNC:25712): (post-GPI attachment to proteins inositol deacylase 1) The protein encoded by this gene functions early in the glycosylphosphatidylinositol (GPI) biosynthetic pathway, catalyzing the inositol deacylation of GPI. The encoded protein is required for the production of GPI that can attach to proteins, and this may be an important factor in the transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi. Defects in this gene are a cause an autosomal recessive form of cognitive impairment. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-196842521-G-GA is Benign according to our data. Variant chr2-196842521-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 1204985.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0154 (2288/148976) while in subpopulation SAS AF= 0.0519 (246/4736). AF 95% confidence interval is 0.0466. There are 24 homozygotes in gnomad4. There are 1138 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGAP1	NM_024989.4	c.2630+199_2630+200insT		intron_variant		ENST00000354764.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP1	ENST00000354764.9	c.2630+199_2630+200insT		intron_variant		1	NM_024989.4	P1

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2290 AN: 148872 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.00376

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0290

Gnomad EAS AF: 0.000391

Gnomad SAS AF: 0.0519

Gnomad FIN AF: 0.00995

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0151

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0154 AC: 2288 AN: 148976 Hom.: 24 Cov.: 32 AF XY: 0.0157 AC XY: 1138 AN XY: 72548

Gnomad4 AFR AF: 0.00374

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.0290

Gnomad4 EAS AF: 0.000392

Gnomad4 SAS AF: 0.0519

Gnomad4 FIN AF: 0.00995

Gnomad4 NFE AF: 0.0214

Gnomad4 OTH AF: 0.0145

Bravo AF: 0.0132

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200071090; hg19: chr2-197707245;