dbSNP rs2278845: PGAP2:c.140-105G>C (chr11-3808189-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001256236.2(PGAP2):c.-32-105G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 1,481,836 control chromosomes in the GnomAD database, including 423,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 34480 hom., cov: 31)

Exomes 𝑓: 0.76 ( 389105 hom. )

Consequence

PGAP2
NM_001256236.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.191

Publications

3 publications found

Variant links:

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

PGAP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 11-3808189-G-C is Benign according to our data. Variant chr11-3808189-G-C is described in ClinVar as Benign. ClinVar VariationId is 1234659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

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

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
PGAP2	NM_001256236.2	c.-32-105G>C	intron	N/A	NP_001243165.2
PGAP2	NM_001346397.2	c.122-105G>C	intron	N/A	NP_001333326.1
PGAP2	NM_001346403.1	c.-33+102G>C	intron	N/A	NP_001333332.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PGAP2	ENST00000300730.10	TSL:1	c.140-105G>C	intron	N/A	ENSP00000300730.6	Q9UHJ9-5
PGAP2	ENST00000396993.8	TSL:1	c.-325-105G>C	intron	N/A	ENSP00000380190.6	A8MZF5
PGAP2	ENST00000465237.6	TSL:1	n.76-105G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.652

AC:

99104

AN:

151902

Hom.:

34490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.729

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.689

Gnomad EAS

AF:

0.770

Gnomad SAS

AF:

0.670

Gnomad FIN

AF:

0.767

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.785

Gnomad OTH

AF:

0.674

GnomAD4 exome

AF:

0.760

AC:

1011280

AN:

1329818

Hom.:

389105

Cov.:

AF XY:

0.759

AC XY:

499607

AN XY:

657986

show subpopulations

African (AFR)

AF:

0.377

AC:

11295

AN:

29986

American (AMR)

AF:

0.586

AC:

20261

AN:

34570

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

16795

AN:

24236

East Asian (EAS)

AF:

0.785

AC:

27466

AN:

34978

South Asian (SAS)

AF:

0.684

AC:

52744

AN:

77118

European-Finnish (FIN)

AF:

0.763

AC:

37184

AN:

48736

Middle Eastern (MID)

AF:

0.589

AC:

3147

AN:

5340

European-Non Finnish (NFE)

AF:

0.787

AC:

802001

AN:

1019486

Other (OTH)

AF:

0.729

AC:

40387

AN:

55368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

11147

22294

33442

44589

55736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18866

37732

56598

75464

94330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.652

AC:

99114

AN:

152018

Hom.:

34480

Cov.:

AF XY:

0.651

AC XY:

48364

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.398

AC:

16488

AN:

41440

American (AMR)

AF:

0.610

AC:

9312

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.689

AC:

2393

AN:

3472

East Asian (EAS)

AF:

0.770

AC:

3979

AN:

5166

South Asian (SAS)

AF:

0.671

AC:

3230

AN:

4814

European-Finnish (FIN)

AF:

0.767

AC:

8098

AN:

10564

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.785

AC:

53365

AN:

67982

Other (OTH)

AF:

0.669

AC:

1408

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1539

3079

4618

6158

7697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.717

Hom.:

5055

Bravo

AF:

0.628

Asia WGS

AF:

0.670

AC:

2329

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.4

(source)

DANN

Benign

0.83

PhyloP100

-0.19

PromoterAI

0.11

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over