chr2-232379003-G-C

Position:

chr2-232379003-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001632.5(ALPP):c.109G>C(p.Glu37Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,613,576 control chromosomes in the GnomAD database, including 229 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 39 hom., cov: 32)

Exomes 𝑓: 0.012 ( 190 hom. )

Consequence

ALPP
NM_001632.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.262

Variant links:

Genes affected

ALPP (HGNC:439): (alkaline phosphatase, placental) The protein encoded by this gene is an alkaline phosphatase, a metalloenzyme that catalyzes the hydrolysis of phosphoric acid monoesters. It belongs to a multigene family composed of four alkaline phosphatase isoenzymes. The enzyme functions as a homodimer and has a catalytic site containing one magnesium and two zinc ions, which are required for its enzymatic function. One of the main sources of this enzyme is the liver, and thus, it's one of several indicators of liver injury in different clinical conditions. In pregnant women, this protein is primarily expressed in placental and endometrial tissue, however, strong ectopic expression has been detected in ovarian adenocarcinoma, serous cystadenocarcinoma, and other ovarian cancer cells. [provided by RefSeq, Aug 2020]

ALPP links:

LOC124906123 (HGNC:):

LOC124906123 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040620863).

BP6

Variant 2-232379003-G-C is Benign according to our data. Variant chr2-232379003-G-C is described in ClinVar as [Benign]. Clinvar id is 773651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0176 (2680/152104) while in subpopulation AFR AF= 0.0345 (1429/41388). AF 95% confidence interval is 0.033. There are 39 homozygotes in gnomad4. There are 1233 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPP	NM_001632.5 link	c.109G>C	p.Glu37Gln	missense_variant	2/11	ENST00000392027.3	NP_001623.3	P05187B2R7C7
LOC124906123	XR_007088121.1 link	n.30C>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPP	ENST00000392027.3 link	c.109G>C	p.Glu37Gln	missense_variant	2/11	1	NM_001632.5	ENSP00000375881.2		P05187
ALPP	ENST00000474529.1 link	n.188G>C		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2679

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00988

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0311

Gnomad SAS

AF:

0.0345

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.0147

AC:

3701

AN:

251054

Hom.:

AF XY:

0.0152

AC XY:

2066

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.00337

Gnomad EAS exome

AF:

0.0347

Gnomad SAS exome

AF:

0.0324

Gnomad FIN exome

AF:

0.00481

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0122

GnomAD4 exome

AF:

0.0121

AC:

17643

AN:

1461472

Hom.:

190

Cov.:

AF XY:

0.0125

AC XY:

9080

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.0335

Gnomad4 AMR exome

AF:

0.00474

Gnomad4 ASJ exome

AF:

0.00344

Gnomad4 EAS exome

AF:

0.0300

Gnomad4 SAS exome

AF:

0.0291

Gnomad4 FIN exome

AF:

0.00440

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.0176

AC:

2680

AN:

152104

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1233

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0345

Gnomad4 AMR

AF:

0.00981

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.0310

Gnomad4 SAS

AF:

0.0343

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.0104

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00320

Hom.:

Bravo

AF:

0.0184

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00701

AC:

ExAC

AF:

0.0160

AC:

1941

EpiCase

AF:

0.00883

EpiControl

AF:

0.00966

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 03, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.080

DANN

Benign

0.83

DEOGEN2

Benign

0.034

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.011

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.5

PrimateAI

Benign

0.43

PROVEAN

Benign

1.6

REVEL

Benign

0.054

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.049

MPC

0.079

ClinPred

0.0070

GERP RS

-0.81

Varity_R

0.15

gMVP

0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over