9-137008487-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001606.5(ABCA2):c.7204G>A(p.Ala2402Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000178 in 1,573,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ABCA2
NM_001606.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

Publications

0 publications found

Variant links:

Genes affected

ABCA2 (HGNC:32): (ATP binding cassette subfamily A member 2) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This protein is highly expressed in brain tissue and may play a role in macrophage lipid metabolism and neural development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ABCA2 Gene-Disease associations (from GenCC):

intellectual developmental disorder with poor growth and with or without seizures or ataxia
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
schizophrenia
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ABCA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2758964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA2	NM_001606.5 link	c.7204G>A	p.Ala2402Thr	missense_variant	Exon 48 of 49	ENST00000341511.11	NP_001597.2	Q9BZC7-3
ABCA2	NM_212533.3 link	c.7294G>A	p.Ala2432Thr	missense_variant	Exon 48 of 49		NP_997698.1	Q9BZC7-4
ABCA2	NM_001411042.1 link	c.7201G>A	p.Ala2401Thr	missense_variant	Exon 47 of 48		NP_001397971.1
ABCA2	XM_047422921.1 link	c.7291G>A	p.Ala2431Thr	missense_variant	Exon 47 of 48		XP_047278877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA2	ENST00000341511.11 link	c.7204G>A	p.Ala2402Thr	missense_variant	Exon 48 of 49	5	NM_001606.5	ENSP00000344155.6		Q9BZC7-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

183298

AF XY:

0.0000202

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000176

AC:

AN:

1420698

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

703226

show subpopulations

African (AFR)

AF:

0.0000307

AC:

AN:

32622

American (AMR)

AF:

0.00

AC:

AN:

38578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25416

East Asian (EAS)

AF:

0.00

AC:

AN:

37574

South Asian (SAS)

AF:

0.000270

AC:

AN:

81376

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091738

Other (OTH)

AF:

0.0000340

AC:

AN:

58822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41560

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000253

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 05, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.7294G>A (p.A2432T) alteration is located in exon 48 (coding exon 48) of the ABCA2 gene. This alteration results from a G to A substitution at nucleotide position 7294, causing the alanine (A) at amino acid position 2432 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

.;T;T;.;T

Eigen

Benign

0.15

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.92

D;D;D;D;D

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.28

T;T;T;T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

1.8

.;L;.;.;.

PhyloP100

4.8

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.53

N;N;N;.;N

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

D;D;D;.;D

Sift4G

Uncertain

0.016

D;D;D;D;T

Polyphen

0.96

.;D;.;.;.

Vest4

0.58

MutPred

0.27

.;Gain of phosphorylation at A2401 (P = 0.0247);.;.;.;

MVP

0.70

MPC

0.66

ClinPred

0.84

GERP RS

3.8

Varity_R

0.078

gMVP

0.47

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

9-137008487-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over