9-137008459-A-C

Variant names:

• chr9-137008459-A-C
• rs1019764433
• NM_001606.5:c.7232T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001606.5(ABCA2):​c.7232T>G​(p.Leu2411Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000568 in 1,407,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: ABCA2 NM_001606.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA2	NM_001606.5	MANE Select	c.7232T>G	p.Leu2411Arg	missense	Exon 48 of 49	NP_001597.2
	ABCA2	NM_212533.3		c.7322T>G	p.Leu2441Arg	missense	Exon 48 of 49	NP_997698.1	Q9BZC7-4
	ABCA2	NM_001411042.1		c.7229T>G	p.Leu2410Arg	missense	Exon 47 of 48	NP_001397971.1	Q9BZC7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA2	ENST00000341511.11	TSL:5 MANE Select	c.7232T>G	p.Leu2411Arg	missense	Exon 48 of 49	ENSP00000344155.6	Q9BZC7-3
	ABCA2	ENST00000459850.5	TSL:1	n.7442T>G		non_coding_transcript_exon	Exon 46 of 47
	ABCA2	ENST00000464157.1	TSL:1	n.222T>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000601 AC: 1 AN: 166384 AF XY: 0.0000112

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: 0.0000149

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000568 AC: 8 AN: 1407812 Hom.: 0 Cov.: 42 AF XY: 0.00000862 AC XY: 6 AN XY: 695742

African (AFR) AF: 0.00 AC: 0 AN: 32132

American (AMR) AF: 0.00 AC: 0 AN: 36778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25246

East Asian (EAS) AF: 0.00 AC: 0 AN: 36576

South Asian (SAS) AF: 0.00 AC: 0 AN: 80248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48102

Middle Eastern (MID) AF: 0.000700 AC: 4 AN: 5716

European-Non Finnish (NFE) AF: 0.00000277 AC: 3 AN: 1084638

Other (OTH) AF: 0.0000171 AC: 1 AN: 58376

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.2
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.71	N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.099	T
Polyphen		0.99	D
Vest4		0.73
MutPred		0.22		Loss of stability (P = 0.0582)
MVP		0.80
MPC		0.99
ClinPred		0.59	D
GERP RS		4.1
Varity_R		0.31
gMVP		0.64
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs1019764433; hg19: chr9-139902911;