Variant 9-137011907-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate

The NM_001606.5(ABCA2):c.5472C>A(p.His1824Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ABCA2
NM_001606.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.82

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:

ABCA2 (HGNC:):

ABCA2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ABCA2. . Gene score misZ 4.9116 (greater than the threshold 3.09). Trascript score misZ 3.725 (greater than threshold 3.09). GenCC has associacion of gene with schizophrenia, intellectual developmental disorder with poor growth and with or without seizures or ataxia.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA2	NM_001606.5 linkuse as main transcript	c.5472C>A	p.His1824Gln	missense_variant	35/49	ENST00000341511.11	NP_001597.2	Q9BZC7-3
ABCA2	NM_212533.3 linkuse as main transcript	c.5562C>A	p.His1854Gln	missense_variant	35/49		NP_997698.1	Q9BZC7-4
ABCA2	NM_001411042.1 linkuse as main transcript	c.5469C>A	p.His1823Gln	missense_variant	34/48		NP_001397971.1
ABCA2	XM_047422921.1 linkuse as main transcript	c.5559C>A	p.His1853Gln	missense_variant	34/48		XP_047278877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA2	ENST00000341511.11 linkuse as main transcript	c.5472C>A	p.His1824Gln	missense_variant	35/49	5	NM_001606.5	ENSP00000344155.6		Q9BZC7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459568

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726024

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Pathogenic

0.85

.;D;D;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.87

D;D;D;D

MetaSVM

Uncertain

0.15

MutationAssessor

Uncertain

2.4

.;M;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-5.9

D;D;D;.

REVEL

Uncertain

0.64

Sift

Uncertain

0.0040

D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.52

.;P;.;.

Vest4

0.85

MutPred

0.38

.;Gain of helix (P = 0.0854);.;.;

MVP

0.87

MPC

1.7

ClinPred

0.98

GERP RS

2.3

Varity_R

0.14

gMVP

0.98

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over