rs908832

Positions:

• chr9-137018032-A-C
• chr9-137018032-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001606.5(ABCA2):​c.2037T>G​(p.Asp679Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCA2 NM_001606.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA2	NM_001606.5	c.2037T>G	p.Asp679Glu	missense_variant	15/49	ENST00000341511.11	NP_001597.2
ABCA2	NM_212533.3	c.2127T>G	p.Asp709Glu	missense_variant	15/49		NP_997698.1
ABCA2	NM_001411042.1	c.2034T>G	p.Asp678Glu	missense_variant	14/48		NP_001397971.1
ABCA2	XM_047422921.1	c.2124T>G	p.Asp708Glu	missense_variant	14/48		XP_047278877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA2	ENST00000341511.11	c.2037T>G	p.Asp679Glu	missense_variant	15/49	5	NM_001606.5	ENSP00000344155.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 84

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	17
DANN	Benign	0.47
DEOGEN2	Benign	0.30	.;T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Pathogenic	0.82	D
MetaRNN	Uncertain	0.46	T;T;T;T
MetaSVM	Uncertain	0.012	D
MutationAssessor	Benign	0.51	.;N;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.30	N;N;N;.
REVEL	Uncertain	0.43
Sift	Benign	1.0	T;T;T;.
Sift4G	Benign	0.89	T;T;T;T
Polyphen		0.98	.;D;.;.
Vest4		0.51
MutPred		0.55		.;Loss of helix (P = 0.1299);.;.;
MVP		0.63
MPC		1.6
ClinPred		0.17	T
GERP RS		-2.8
Varity_R		0.20
gMVP		0.91

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

LitVar

Other links and lift over

dbSNP: rs908832; hg19: chr9-139912484;