11-3807994-C-T

Variant summary

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

The ENST00000300730.10(PGAP2):c.140-300C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,288,526 control chromosomes in the GnomAD database, including 9,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.095 (868 hom., cov: 30)
  • Exomes 𝑓: 0.12 (8649 hom.)
• Consequence: PGAP2 ENST00000300730.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.20

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=-0.89).
• BP6: Variant 11-3807994-C-T is Benign according to our data. Variant chr11-3807994-C-T is described in ClinVar as [Benign]. Clinvar id is 1182903.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGAP2	NM_001145438.2	c.140-300C>T		intron_variant
PGAP2	NM_001256235.1	c.-63-300C>T		intron_variant
PGAP2	NM_001256236.1	c.140-300C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP2	ENST00000300730.10	c.140-300C>T		intron_variant		1
PGAP2	ENST00000396993.8	c.-325-300C>T		intron_variant		1
PGAP2	ENST00000528216.5	c.-32-300C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14385 AN: 152050 Hom.: 869 Cov.: 30

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.119 AC: 135052 AN: 1136358 Hom.: 8649 Cov.: 18 AF XY: 0.118 AC XY: 64289 AN XY: 546362

Gnomad4 AFR exome AF: 0.0335

Gnomad4 AMR exome AF: 0.0971

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.0581

Gnomad4 FIN exome AF: 0.0890

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.0945 AC: 14382 AN: 152168 Hom.: 868 Cov.: 30 AF XY: 0.0930 AC XY: 6920 AN XY: 74406

Gnomad4 AFR AF: 0.0367

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0512

Gnomad4 FIN AF: 0.0916

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0763 Hom.: 114

Bravo AF: 0.0945

Asia WGS AF: 0.0260 AC: 92 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

Sep 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.045
Dann	Benign	0.70

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: rs72844341; hg19: chr11-3829224;