11-3811027-G-T

Variant names:

• chr11-3811027-G-T
• rs2898938
• NM_014489.4:c.-10-223G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

PGAP2 Gene-Disease associations (from GenCC):

• hyperphosphatasia with intellectual disability syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hyperphosphatasia-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124902618 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014489.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGAP2	NM_014489.4	MANE Select	c.-10-223G>T		intron	N/A	NP_055304.1	Q9UHJ9-2
	PGAP2	NM_001256236.2		c.-10-223G>T		intron	N/A	NP_001243165.2
	PGAP2	NM_001346397.2		c.144-223G>T		intron	N/A	NP_001333326.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGAP2	ENST00000278243.9	TSL:1 MANE Select	c.-10-223G>T		intron	N/A	ENSP00000278243.4	Q9UHJ9-2
	PGAP2	ENST00000300730.10	TSL:1	c.162-223G>T		intron	N/A	ENSP00000300730.6	Q9UHJ9-5
	PGAP2	ENST00000396993.8	TSL:1	c.-304+2712G>T		intron	N/A	ENSP00000380190.6	A8MZF5

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

African (AFR) AF: 0.297 AC: 12322 AN: 41484

American (AMR) AF: 0.578 AC: 8834 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2322 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4060 AN: 5176

South Asian (SAS) AF: 0.682 AC: 3285 AN: 4820

European-Finnish (FIN) AF: 0.787 AC: 8327 AN: 10578

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.739 AC: 50231 AN: 67992

Other (OTH) AF: 0.634 AC: 1337 AN: 2110

Alfa AF: 0.644 Hom.: 6396

Bravo AF: 0.569

Asia WGS AF: 0.697 AC: 2424 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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