Variant 2-196897152-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_024989.4(PGAP1):c.906T>C(p.Leu302=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0047 in 1,578,116 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 22 hom. )

Consequence

PGAP1
NM_024989.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.850

Variant links:

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]

PGAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 2-196897152-A-G is Benign according to our data. Variant chr2-196897152-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 436295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-196897152-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.85 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0027 (412/152328) while in subpopulation NFE AF= 0.00479 (326/68012). AF 95% confidence interval is 0.00437. There are 1 homozygotes in gnomad4. There are 194 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP1	NM_024989.4 linkuse as main transcript	c.906T>C	p.Leu302=	synonymous_variant	7/27	ENST00000354764.9	NP_079265.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGAP1	ENST00000354764.9 linkuse as main transcript	c.906T>C	p.Leu302=	synonymous_variant	7/27	1	NM_024989.4	ENSP00000346809	P1	Q75T13-1

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

412

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00479

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00220

AC:

513

AN:

233676

Hom.:

AF XY:

0.00219

AC XY:

277

AN XY:

126262

show subpopulations

Gnomad AFR exome

AF:

0.000899

Gnomad AMR exome

AF:

0.000824

Gnomad ASJ exome

AF:

0.00266

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000641

Gnomad FIN exome

AF:

0.000655

Gnomad NFE exome

AF:

0.00377

Gnomad OTH exome

AF:

0.00175

GnomAD4 exome

AF:

0.00492

AC:

7011

AN:

1425788

Hom.:

Cov.:

AF XY:

0.00467

AC XY:

3317

AN XY:

709536

show subpopulations

Gnomad4 AFR exome

AF:

0.000775

Gnomad4 AMR exome

AF:

0.000704

Gnomad4 ASJ exome

AF:

0.00271

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.000987

Gnomad4 FIN exome

AF:

0.00104

Gnomad4 NFE exome

AF:

0.00591

Gnomad4 OTH exome

AF:

0.00530

GnomAD4 genome

AF:

0.00270

AC:

412

AN:

152328

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

194

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00479

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00375

Hom.:

Bravo

AF:

0.00279

Asia WGS

AF:

0.000289

AC:

AN:

3468

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 22, 2016

- -

Hereditary spastic paraplegia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 04, 2022

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

PGAP1: BP4, BP7 -

Intellectual disability, autosomal recessive 42

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.7

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over