Genetic Variant ABCA2:n.168G>C (chr9-137028748-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_212533.3(ABCA2):c.125G>C(p.Arg42Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000887 in 1,127,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/11 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. R42Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

ABCA2
NM_212533.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.19

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 links:

LINC02908 (HGNC:31426): (long intergenic non-protein coding RNA 2908)

LINC02908 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038533688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
ABCA2	NM_212533.3 link	c.125G>C	p.Arg42Pro	missense_variant	Exon 1 of 49	NP_997698.1	Q9BZC7-4
ABCA2	XM_047422921.1 link	c.125G>C	p.Arg42Pro	missense_variant	Exon 1 of 48	XP_047278877.1
LINC02908	NR_171031.1 link	n.448+837C>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
ABCA2	ENST00000459850.5 link	n.168G>C		non_coding_transcript_exon_variant	Exon 1 of 47	1
ABCA2	ENST00000487109.5 link	n.125G>C		non_coding_transcript_exon_variant	Exon 1 of 47	1	ENSP00000418662.1	E9PGB2
ABCA2	ENST00000614293.5 link	c.125G>C	p.Arg42Pro	missense_variant	Exon 1 of 49	5	ENSP00000481105.2	Q9BZC7-4A0A087WXK5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000620

AC:

AN:

161222

AF XY:

0.0000109

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:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

8.87e-7

AC:

AN:

1127032

Hom.:

Cov.:

AF XY:

0.00000180

AC XY:

AN XY:

555596

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20320

American (AMR)

AF:

0.00

AC:

AN:

17384

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13698

East Asian (EAS)

AF:

0.00

AC:

AN:

10530

South Asian (SAS)

AF:

0.00

AC:

AN:

70078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30170

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4156

European-Non Finnish (NFE)

AF:

0.00000109

AC:

AN:

920502

Other (OTH)

AF:

0.00

AC:

AN:

40194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.9

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.26

.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.37

T;T

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-1.1

PhyloP100

-3.2

Sift4G

Benign

0.29

T;.

Vest4

0.098

MVP

0.043

ClinPred

0.045

GERP RS

-2.2

PromoterAI

-0.0032

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over