11-3811027-G-T

Variant summary

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

The NM_014489.4(PGAP2):c.-10-223G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,120 control chromosomes in the GnomAD database, including 30,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.60 (30523 hom., cov: 32)
• Consequence: PGAP2 NM_014489.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.382

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=-0.75).
• BP6: Variant 11-3811027-G-T is Benign according to our data. Variant chr11-3811027-G-T is described in ClinVar as [Benign]. Clinvar id is 1236447.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGAP2	NM_014489.4	c.-10-223G>T		intron_variant		ENST00000278243.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP2	ENST00000278243.9	c.-10-223G>T		intron_variant		1	NM_014489.4	A1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91470 AN: 152004 Hom.: 30528 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.601 AC: 91484 AN: 152120 Hom.: 30523 Cov.: 32 AF XY: 0.603 AC XY: 44826 AN XY: 74354

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.634

Alfa AF: 0.644 Hom.: 6396

Bravo AF: 0.569

Asia WGS AF: 0.697 AC: 2424 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	-0.75
Cadd	Benign	13
Dann	Benign	0.77

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: rs2898938; hg19: chr11-3832257; COSMIC: COSV53465523; COSMIC: COSV53465523;