11-3808632-C-G

Position:

• chr11-3808632-C-G

Variant summary

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

The NM_014489.4(PGAP2):​c.-30C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,293,316 control chromosomes in the GnomAD database, including 9,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (850 hom., cov: 32)
  • Exomes 𝑓: 0.12 (8576 hom.)
• Consequence: PGAP2 NM_014489.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.768

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=-0.88).
• BP6: Variant 11-3808632-C-G is Benign according to our data. Variant chr11-3808632-C-G is described in ClinVar as [Benign]. Clinvar id is 1279122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGAP2	NM_014489.4	c.-30C>G		5_prime_UTR_variant	1/7	ENST00000278243.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP2	ENST00000278243.9	c.-30C>G		5_prime_UTR_variant	1/7	1	NM_014489.4	A1

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13748 AN: 152122 Hom.: 851 Cov.: 32

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0505

Gnomad FIN AF: 0.0923

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.118 AC: 134696 AN: 1141076 Hom.: 8576 Cov.: 30 AF XY: 0.117 AC XY: 64153 AN XY: 549132

Gnomad4 AFR exome AF: 0.0190

Gnomad4 AMR exome AF: 0.0987

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.000571

Gnomad4 SAS exome AF: 0.0598

Gnomad4 FIN exome AF: 0.0896

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.0903 AC: 13744 AN: 152240 Hom.: 850 Cov.: 32 AF XY: 0.0887 AC XY: 6606 AN XY: 74438

Gnomad4 AFR AF: 0.0230

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.0510

Gnomad4 FIN AF: 0.0923

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0473 Hom.: 47

Bravo AF: 0.0896

Asia WGS AF: 0.0270 AC: 94 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	-0.88
CADD	Benign	2.8
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs61896956; hg19: chr11-3829862;