chr9-137008538-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001606.5(ABCA2):c.7153G>A(p.Gly2385Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,602,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2385R) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

ABCA2
NM_001606.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09

Publications

1 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14625955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA2	NM_001606.5 link	c.7153G>A	p.Gly2385Ser	missense_variant	Exon 48 of 49	ENST00000341511.11	NP_001597.2	Q9BZC7-3
ABCA2	NM_212533.3 link	c.7243G>A	p.Gly2415Ser	missense_variant	Exon 48 of 49		NP_997698.1	Q9BZC7-4
ABCA2	NM_001411042.1 link	c.7150G>A	p.Gly2384Ser	missense_variant	Exon 47 of 48		NP_001397971.1
ABCA2	XM_047422921.1 link	c.7240G>A	p.Gly2414Ser	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.7153G>A	p.Gly2385Ser	missense_variant	Exon 48 of 49	5	NM_001606.5	ENSP00000344155.6		Q9BZC7-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000394

AC:

AN:

228498

AF XY:

0.0000322

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000910

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000486

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000262

AC:

AN:

1450300

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

720308

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33330

American (AMR)

AF:

0.000115

AC:

AN:

43544

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25908

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39258

South Asian (SAS)

AF:

0.0000475

AC:

AN:

84196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50970

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000235

AC:

AN:

1107414

Other (OTH)

AF:

0.00

AC:

AN:

59926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000417

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.38

CADD

Benign

8.7

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.27

.;T;T;.;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.67

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.74

T;T;T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

0.34

.;N;.;.;.

PhyloP100

1.1

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.14

N;N;N;.;N

REVEL

Benign

0.21

Sift

Benign

0.63

T;T;T;.;T

Sift4G

Benign

0.57

T;T;T;T;T

Polyphen

0.0040

.;B;.;.;.

Vest4

0.14

MutPred

0.32

.;Loss of sheet (P = 0.0025);.;.;.;

MVP

0.37

MPC

0.68

ClinPred

0.054

GERP RS

3.2

Varity_R

0.037

gMVP

0.24

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr9-137008538-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over