11-3808066-CCGG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000300730.10(PGAP2):c.140-227_140-225del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,423,458 control chromosomes in the GnomAD database, including 10,405 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (850 hom., cov: 28)
  • Exomes 𝑓: 0.12 (9555 hom.)
• Consequence: PGAP2 ENST00000300730.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0300

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 -10 ACMG points.

• BP6: Variant 11-3808066-CCGG-C is Benign according to our data. Variant chr11-3808066-CCGG-C is described in ClinVar as [Benign]. Clinvar id is 1220981.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGAP2	NM_001256238.1	c.-53_-51del		5_prime_UTR_variant	1/7
PGAP2	NM_001346403.1	c.-53_-51del		5_prime_UTR_variant	1/8
PGAP2	NM_001346404.1	c.-53_-51del		5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP2	ENST00000300730.10	c.140-227_140-225del		intron_variant		1
PGAP2	ENST00000396993.8	c.-325-227_-325-225del		intron_variant		1
PGAP2	ENST00000528216.5	c.-32-227_-32-225del		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13782 AN: 152106 Hom.: 851 Cov.: 28

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.118 AC: 149820 AN: 1271234 Hom.: 9555 AF XY: 0.117 AC XY: 71950 AN XY: 616764

Gnomad4 AFR exome AF: 0.0200

Gnomad4 AMR exome AF: 0.0990

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.000441

Gnomad4 SAS exome AF: 0.0596

Gnomad4 FIN exome AF: 0.0926

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.0905 AC: 13778 AN: 152224 Hom.: 850 Cov.: 28 AF XY: 0.0889 AC XY: 6619 AN XY: 74432

Gnomad4 AFR AF: 0.0231

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0505

Gnomad4 FIN AF: 0.0917

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.115

Alfa AF: 0.105 Hom.: 116

Bravo AF: 0.0901

Asia WGS AF: 0.0260 AC: 90 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

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: rs75108073; hg19: chr11-3829296; COSMIC: COSV53463763; COSMIC: COSV53463763;