11-3798189-T-A

Variant summary

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

The ENST00000300730.10(PGAP2):c.139+207T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,298,778 control chromosomes in the GnomAD database, including 8,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (979 hom., cov: 33)
  • Exomes 𝑓: 0.11 (7132 hom.)
• Consequence: PGAP2 ENST00000300730.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0870

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=-0.73).
• BP6: Variant 11-3798189-T-A is Benign according to our data. Variant chr11-3798189-T-A is described in ClinVar as [Benign]. Clinvar id is 1238749.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGAP2	NM_001145438.2	c.139+207T>A		intron_variant
PGAP2	NM_001256235.1	c.-64+446T>A		intron_variant
PGAP2	NM_001256236.1	c.139+207T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP2	ENST00000300730.10	c.139+207T>A		intron_variant		1
PGAP2	ENST00000396993.8	c.-326+207T>A		intron_variant		1
PGAP2	ENST00000528216.5	c.-33+446T>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16435 AN: 152074 Hom.: 977 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.108 AC: 124137 AN: 1146586 Hom.: 7132 AF XY: 0.107 AC XY: 59296 AN XY: 555240

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.0907

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.000218

Gnomad4 SAS exome AF: 0.0425

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.108 AC: 16455 AN: 152192 Hom.: 979 Cov.: 33 AF XY: 0.107 AC XY: 7954 AN XY: 74420

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.120

Alfa AF: 0.112 Hom.: 119

Bravo AF: 0.110

Asia WGS AF: 0.0230 AC: 79 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	4.7
Dann	Benign	0.62

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: rs7105207; hg19: chr11-3819419;