11-3808189-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000300730.10(PGAP2):c.140-105G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 1,481,836 control chromosomes in the GnomAD database, including 423,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (34480 hom., cov: 31)
  • Exomes 𝑓: 0.76 (389105 hom.)
• Consequence: PGAP2 ENST00000300730.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.191

Genes affected

PGAP2 (HGNC:17893): (post-GPI attachment to proteins 2) The protein encoded by this gene plays a role in the maturation of glycosylphosphatidylinositol (GPI) anchors on GPI-anchored proteins. Mutations in this gene are associated with an autosomal recessive syndrome characterized by hyperphosphatasia and intellectual disability. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 11-3808189-G-C is Benign according to our data. Variant chr11-3808189-G-C is described in ClinVar as [Benign]. Clinvar id is 1234659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGAP2	NM_001145438.2	c.140-105G>C		intron_variant
PGAP2	NM_001256235.1	c.-63-105G>C		intron_variant
PGAP2	NM_001256236.1	c.140-105G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP2	ENST00000300730.10	c.140-105G>C		intron_variant		1
PGAP2	ENST00000396993.8	c.-325-105G>C		intron_variant		1
PGAP2	ENST00000528216.5	c.-32-105G>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99104 AN: 151902 Hom.: 34490 Cov.: 31

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.674

GnomAD4 exome AF: 0.760 AC: 1011280 AN: 1329818 Hom.: 389105 Cov.: 19 AF XY: 0.759 AC XY: 499607 AN XY: 657986

Gnomad4 AFR exome AF: 0.377

Gnomad4 AMR exome AF: 0.586

Gnomad4 ASJ exome AF: 0.693

Gnomad4 EAS exome AF: 0.785

Gnomad4 SAS exome AF: 0.684

Gnomad4 FIN exome AF: 0.763

Gnomad4 NFE exome AF: 0.787

Gnomad4 OTH exome AF: 0.729

GnomAD4 genome AF: 0.652 AC: 99114 AN: 152018 Hom.: 34480 Cov.: 31 AF XY: 0.651 AC XY: 48364 AN XY: 74298

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.669

Alfa AF: 0.717 Hom.: 5055

Bravo AF: 0.628

Asia WGS AF: 0.670 AC: 2329 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	6.4
Dann	Benign	0.83

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: rs2278845; hg19: chr11-3829419; COSMIC: COSV53464127; COSMIC: COSV53464127;