chr2-196841029-C-G

Position:

• chr2-196841029-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024989.4(PGAP1):​c.*205G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 542,230 control chromosomes in the GnomAD database, including 2,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1258 hom., cov: 32)
  • Exomes 𝑓: 0.084 (1717 hom.)
• Consequence: PGAP1 NM_024989.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.315

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 2-196841029-C-G is Benign according to our data. Variant chr2-196841029-C-G is described in ClinVar as [Benign]. Clinvar id is 1275518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGAP1	NM_024989.4	c.*205G>C		3_prime_UTR_variant	27/27	ENST00000354764.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP1	ENST00000354764.9	c.*205G>C		3_prime_UTR_variant	27/27	1	NM_024989.4	P1
PGAP1	ENST00000423035.5	c.*2905G>C		3_prime_UTR_variant, NMD_transcript_variant	28/28	1
PGAP1	ENST00000422444.1	c.*205G>C		3_prime_UTR_variant	4/4	2
PGAP1	ENST00000459896.5	n.105+1692G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17195 AN: 152080 Hom.: 1256 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0723

Gnomad OTH AF: 0.0976

GnomAD4 exome AF: 0.0845 AC: 32945 AN: 390032 Hom.: 1717 Cov.: 6 AF XY: 0.0871 AC XY: 17619 AN XY: 202356

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.0603

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.0562

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.0784

Gnomad4 NFE exome AF: 0.0734

Gnomad4 OTH exome AF: 0.0938

GnomAD4 genome AF: 0.113 AC: 17211 AN: 152198 Hom.: 1258 Cov.: 32 AF XY: 0.113 AC XY: 8374 AN XY: 74430

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.0665

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.0568

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0802

Gnomad4 NFE AF: 0.0723

Gnomad4 OTH AF: 0.101

Alfa AF: 0.102 Hom.: 129

Bravo AF: 0.115

Asia WGS AF: 0.123 AC: 429 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.77
DANN	Benign	0.43

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: rs59749746; hg19: chr2-197705753;