ENST00000300730.10:c.140-300C>T

Variant names:

• chr11-3807994-C-T
• rs72844341
• ENST00000300730.10:c.140-300C>T

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.140-300C>T 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 1,288,526 control chromosomes in the GnomAD database, including 9,517 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 (8649 hom.)
• Consequence: PGAP2 ENST00000300730.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.20
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-3807994-C-T is Benign according to our data. Variant chr11-3807994-C-T is described in ClinVar as Benign. ClinVar VariationId is 1182903.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.

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.-32-300C>T		intron	N/A	NP_001243165.2
	PGAP2	NM_001346397.2		c.122-300C>T		intron	N/A	NP_001333326.1
	PGAP2	NM_001346402.2		c.4-300C>T		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.140-300C>T		intron	N/A	ENSP00000300730.6	Q9UHJ9-5
	PGAP2	ENST00000396993.8	TSL:1	c.-325-300C>T		intron	N/A	ENSP00000380190.6	A8MZF5
	PGAP2	ENST00000465237.6	TSL:1	n.76-300C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14385 AN: 152050 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: 0.000962

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.119 AC: 135052 AN: 1136358 Hom.: 8649 Cov.: 18 AF XY: 0.118 AC XY: 64289 AN XY: 546362

African (AFR) AF: 0.0335 AC: 824 AN: 24570

American (AMR) AF: 0.0971 AC: 1384 AN: 14258

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 1830 AN: 14686

East Asian (EAS) AF: 0.000403 AC: 10 AN: 24820

South Asian (SAS) AF: 0.0581 AC: 2983 AN: 51342

European-Finnish (FIN) AF: 0.0890 AC: 1743 AN: 19586

Middle Eastern (MID) AF: 0.149 AC: 451 AN: 3018

European-Non Finnish (NFE) AF: 0.129 AC: 121001 AN: 938636

Other (OTH) AF: 0.106 AC: 4826 AN: 45442

GnomAD4 genome AF: 0.0945 AC: 14382 AN: 152168 Hom.: 868 Cov.: 30 AF XY: 0.0930 AC XY: 6920 AN XY: 74406

African (AFR) AF: 0.0367 AC: 1525 AN: 41518

American (AMR) AF: 0.114 AC: 1742 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0512 AC: 247 AN: 4828

European-Finnish (FIN) AF: 0.0916 AC: 971 AN: 10598

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8971 AN: 67974

Other (OTH) AF: 0.118 AC: 249 AN: 2110

Alfa AF: 0.0763 Hom.: 114

Bravo AF: 0.0945

Asia WGS AF: 0.0260 AC: 92 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	-0.89
CADD	Benign	0.045
DANN	Benign	0.70
PhyloP100		-2.2
PromoterAI		-0.11	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: rs72844341; hg19: chr11-3829224;