11-3807993-A-C

Position:

• chr11-3807993-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000300730.10(PGAP2):​c.140-301A>C 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 1,283,006 control chromosomes in the GnomAD database, including 9,500 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 (8632 hom.)
• Consequence: PGAP2 ENST00000300730.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.85

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-3807993-A-C is Benign according to our data. Variant chr11-3807993-A-C is described in ClinVar as [Benign]. Clinvar id is 1289378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.140-301A>C		intron_variant
PGAP2	NM_001256235.1	c.-63-301A>C		intron_variant
PGAP2	NM_001256236.1	c.140-301A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP2	ENST00000300730.10	c.140-301A>C		intron_variant		1
PGAP2	ENST00000396993.8	c.-325-301A>C		intron_variant		1
PGAP2	ENST00000528216.5	c.-32-301A>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14384 AN: 151988 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: 0.000964

Gnomad SAS AF: 0.0508

Gnomad FIN AF: 0.0918

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.119 AC: 134559 AN: 1130900 Hom.: 8632 Cov.: 18 AF XY: 0.118 AC XY: 64035 AN XY: 543616

Gnomad4 AFR exome AF: 0.0336

Gnomad4 AMR exome AF: 0.0976

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.000409

Gnomad4 SAS exome AF: 0.0584

Gnomad4 FIN exome AF: 0.0895

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.0945 AC: 14381 AN: 152106 Hom.: 868 Cov.: 30 AF XY: 0.0930 AC XY: 6918 AN XY: 74360

Gnomad4 AFR AF: 0.0367

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0513

Gnomad4 FIN AF: 0.0918

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.118

Alfa AF: 0.109 Hom.: 123

Bravo AF: 0.0945

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs75453245; hg19: chr11-3829223;