rs72844341

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-3807994-C-A
• chr11-3807994-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001256236.2(PGAP2):​c.-32-300C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PGAP2 NM_001256236.2 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256236.2. 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>A		intron	N/A	NP_001243165.2
	PGAP2	NM_001346397.2		c.122-300C>A		intron	N/A	NP_001333326.1
	PGAP2	NM_001346402.2		c.4-300C>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.140-300C>A		intron	N/A	ENSP00000300730.6	Q9UHJ9-5
	PGAP2	ENST00000396993.8	TSL:1	c.-325-300C>A		intron	N/A	ENSP00000380190.6	A8MZF5
	PGAP2	ENST00000465237.6	TSL:1	n.76-300C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1137298 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 546810

African (AFR) AF: 0.00 AC: 0 AN: 24580

American (AMR) AF: 0.00 AC: 0 AN: 14274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14698

East Asian (EAS) AF: 0.00 AC: 0 AN: 24820

South Asian (SAS) AF: 0.00 AC: 0 AN: 51370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3018

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 939454

Other (OTH) AF: 0.00 AC: 0 AN: 45478

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.026
DANN	Benign	0.56
PhyloP100		-2.2
PromoterAI		-0.099	Neutral

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;