9-137008510-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001606.5(ABCA2):c.7181G>A(p.Arg2394Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00118 in 1,586,100 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

ABCA2
NM_001606.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 5.86

Publications

5 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042449564).

BS2

High Homozygotes in GnomAdExome4 at 3 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001606.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCA2	NM_001606.5	MANE Select	c.7181G>A	p.Arg2394Gln	missense	Exon 48 of 49	NP_001597.2
ABCA2	NM_212533.3		c.7271G>A	p.Arg2424Gln	missense	Exon 48 of 49	NP_997698.1	Q9BZC7-4
ABCA2	NM_001411042.1		c.7178G>A	p.Arg2393Gln	missense	Exon 47 of 48	NP_001397971.1	Q9BZC7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCA2	ENST00000341511.11	TSL:5 MANE Select	c.7181G>A	p.Arg2394Gln	missense	Exon 48 of 49	ENSP00000344155.6	Q9BZC7-3
ABCA2	ENST00000459850.5	TSL:1	n.7391G>A		non_coding_transcript_exon	Exon 46 of 47
ABCA2	ENST00000464157.1	TSL:1	n.171G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.000736

AC:

112

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000609

AC:

123

AN:

202012

AF XY:

0.000621

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000200

Gnomad ASJ exome

AF:

0.000109

Gnomad EAS exome

AF:

0.000267

Gnomad FIN exome

AF:

0.000118

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.000970

GnomAD4 exome

AF:

0.00123

AC:

1766

AN:

1433768

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

856

AN XY:

710598

show subpopulations

African (AFR)

AF:

0.0000303

AC:

AN:

33028

American (AMR)

AF:

0.000343

AC:

AN:

40814

Ashkenazi Jewish (ASJ)

AF:

0.0000390

AC:

AN:

25616

East Asian (EAS)

AF:

0.000339

AC:

AN:

38354

South Asian (SAS)

AF:

0.0000243

AC:

AN:

82468

European-Finnish (FIN)

AF:

0.0000807

AC:

AN:

49590

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00149

AC:

1640

AN:

1098812

Other (OTH)

AF:

0.00152

AC:

AN:

59348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

118

236

354

472

590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.000735

AC:

112

AN:

152332

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41574

American (AMR)

AF:

0.000850

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00128

AC:

AN:

68030

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000889

Hom.:

Bravo

AF:

0.000842

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00156

AC:

ExAC

AF:

0.000461

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

Eigen

Benign

0.11

Eigen_PC

Benign

0.044

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.042

MetaSVM

Uncertain

0.29

MutationAssessor

Benign

1.8

PhyloP100

5.9

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.27

REVEL

Benign

0.28

Sift

Uncertain

0.029

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.47

MVP

0.72

MPC

0.78

ClinPred

0.081

GERP RS

3.8

Varity_R

0.18

gMVP

0.52

Mutation Taster

=90/10

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

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