Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001606.5(ABCA2):c.5472C>T(p.His1824His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,611,604 control chromosomes in the GnomAD database, including 379,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34188 hom., cov: 33)

Exomes 𝑓: 0.69 ( 345043 hom. )

Consequence

ABCA2
NM_001606.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.82

Publications

31 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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 9-137011907-G-A is Benign according to our data. Variant chr9-137011907-G-A is described in ClinVar as Benign. ClinVar VariationId is 1098723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.82 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

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
ABCA2	NM_001606.5	MANE Select	c.5472C>T	p.His1824His	synonymous	Exon 35 of 49	NP_001597.2
ABCA2	NM_212533.3		c.5562C>T	p.His1854His	synonymous	Exon 35 of 49	NP_997698.1
ABCA2	NM_001411042.1		c.5469C>T	p.His1823His	synonymous	Exon 34 of 48	NP_001397971.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCA2	ENST00000341511.11	TSL:5 MANE Select	c.5472C>T	p.His1824His	synonymous	Exon 35 of 49	ENSP00000344155.6
ABCA2	ENST00000459850.5	TSL:1	n.5602C>T		non_coding_transcript_exon	Exon 34 of 47
ABCA2	ENST00000479446.5	TSL:1	n.3519C>T		non_coding_transcript_exon	Exon 22 of 35	ENSP00000420084.1

Frequencies

GnomAD3 genomes

AF:

0.669

AC:

101680

AN:

151994

Hom.:

34170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.707

Gnomad AMR

AF:

0.613

Gnomad ASJ

AF:

0.709

Gnomad EAS

AF:

0.808

Gnomad SAS

AF:

0.748

Gnomad FIN

AF:

0.643

Gnomad MID

AF:

0.656

Gnomad NFE

AF:

0.689

Gnomad OTH

AF:

0.678

GnomAD2 exomes

AF:

0.674

AC:

165665

AN:

245744

AF XY:

0.684

show subpopulations

Gnomad AFR exome

AF:

0.627

Gnomad AMR exome

AF:

0.517

Gnomad ASJ exome

AF:

0.709

Gnomad EAS exome

AF:

0.809

Gnomad FIN exome

AF:

0.655

Gnomad NFE exome

AF:

0.689

Gnomad OTH exome

AF:

0.684

GnomAD4 exome

AF:

0.686

AC:

1001341

AN:

1459492

Hom.:

345043

Cov.:

AF XY:

0.688

AC XY:

499289

AN XY:

725998

show subpopulations

African (AFR)

AF:

0.626

AC:

20946

AN:

33464

American (AMR)

AF:

0.532

AC:

23668

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.711

AC:

18583

AN:

26126

East Asian (EAS)

AF:

0.812

AC:

32194

AN:

39672

South Asian (SAS)

AF:

0.742

AC:

63967

AN:

86184

European-Finnish (FIN)

AF:

0.661

AC:

34349

AN:

51986

Middle Eastern (MID)

AF:

0.661

AC:

3807

AN:

5762

European-Non Finnish (NFE)

AF:

0.686

AC:

762115

AN:

1111446

Other (OTH)

AF:

0.691

AC:

41712

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

21575

43149

64724

86298

107873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19472

38944

58416

77888

97360

<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:

0.669

AC:

101736

AN:

152112

Hom.:

34188

Cov.:

AF XY:

0.668

AC XY:

49680

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.631

AC:

26179

AN:

41482

American (AMR)

AF:

0.613

AC:

9370

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.709

AC:

2459

AN:

3470

East Asian (EAS)

AF:

0.808

AC:

4169

AN:

5160

South Asian (SAS)

AF:

0.749

AC:

3614

AN:

4828

European-Finnish (FIN)

AF:

0.643

AC:

6817

AN:

10594

Middle Eastern (MID)

AF:

0.658

AC:

192

AN:

292

European-Non Finnish (NFE)

AF:

0.689

AC:

46855

AN:

67984

Other (OTH)

AF:

0.681

AC:

1438

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1779

3558

5336

7115

8894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<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:

0.687

Hom.:

109050

Bravo

AF:

0.664

Asia WGS

AF:

0.753

AC:

2617

AN:

3478

EpiCase

AF:

0.701

EpiControl

AF:

0.704

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Intellectual developmental disorder with poor growth and with or without seizures or ataxia (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.4

(source)

DANN

Benign

0.38

PhyloP100

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=94/6

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over