ENST00000300730.10:c.139+207T>A

Variant names:

• chr11-3798189-T-A
• rs7105207
• ENST00000300730.10:c.139+207T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000300730.10(PGAP2):​c.139+207T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,298,778 control chromosomes in the GnomAD database, including 8,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (979 hom., cov: 33)
  • Exomes 𝑓: 0.11 (7132 hom.)
• Consequence: PGAP2 ENST00000300730.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0870
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 11-3798189-T-A is Benign according to our data. Variant chr11-3798189-T-A is described in ClinVar as Benign. ClinVar VariationId is 1238749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000300730.10. 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_001256236.2		c.-33+207T>A		intron	N/A	NP_001243165.2
	PGAP2	NM_001346397.2		c.121+89T>A		intron	N/A	NP_001333326.1
	PGAP2	NM_001346402.2		c.3+207T>A		intron	N/A	NP_001333331.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGAP2	ENST00000300730.10	TSL:1	c.139+207T>A		intron	N/A	ENSP00000300730.6	Q9UHJ9-5
	PGAP2	ENST00000396993.8	TSL:1	c.-326+207T>A		intron	N/A	ENSP00000380190.6	A8MZF5
	PGAP2	ENST00000465237.6	TSL:1	n.75+207T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16435 AN: 152074 Hom.: 977 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.108 AC: 124137 AN: 1146586 Hom.: 7132 AF XY: 0.107 AC XY: 59296 AN XY: 555240

African (AFR) AF: 0.110 AC: 2513 AN: 22926

American (AMR) AF: 0.0907 AC: 1055 AN: 11628

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 2312 AN: 17026

East Asian (EAS) AF: 0.000218 AC: 6 AN: 27468

South Asian (SAS) AF: 0.0425 AC: 2155 AN: 50740

European-Finnish (FIN) AF: 0.120 AC: 3437 AN: 28646

Middle Eastern (MID) AF: 0.125 AC: 413 AN: 3316

European-Non Finnish (NFE) AF: 0.115 AC: 107294 AN: 936678

Other (OTH) AF: 0.103 AC: 4952 AN: 48158

GnomAD4 genome AF: 0.108 AC: 16455 AN: 152192 Hom.: 979 Cov.: 33 AF XY: 0.107 AC XY: 7954 AN XY: 74420

African (AFR) AF: 0.111 AC: 4611 AN: 41514

American (AMR) AF: 0.105 AC: 1600 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4828

European-Finnish (FIN) AF: 0.120 AC: 1269 AN: 10600

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7918 AN: 68012

Other (OTH) AF: 0.120 AC: 254 AN: 2112

Alfa AF: 0.112 Hom.: 119

Bravo AF: 0.110

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.7
DANN	Benign	0.62
PhyloP100		-0.087
PromoterAI		-0.047	Neutral
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: rs7105207; hg19: chr11-3819419;