chr9-137008510-C-G

Variant names:

• chr9-137008510-C-G
• rs55971316
• NM_001606.5:c.7181G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001606.5(ABCA2):​c.7181G>C​(p.Arg2394Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,433,770 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ABCA2 NM_001606.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA2	NM_001606.5	c.7181G>C	p.Arg2394Pro	missense_variant	Exon 48 of 49	ENST00000341511.11	NP_001597.2
ABCA2	NM_212533.3	c.7271G>C	p.Arg2424Pro	missense_variant	Exon 48 of 49		NP_997698.1
ABCA2	NM_001411042.1	c.7178G>C	p.Arg2393Pro	missense_variant	Exon 47 of 48		NP_001397971.1
ABCA2	XM_047422921.1	c.7268G>C	p.Arg2423Pro	missense_variant	Exon 47 of 48		XP_047278877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA2	ENST00000341511.11	c.7181G>C	p.Arg2394Pro	missense_variant	Exon 48 of 49	5	NM_001606.5	ENSP00000344155.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000495 AC: 1 AN: 202012 Hom.: 0 AF XY: 0.00000913 AC XY: 1 AN XY: 109544

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 SAS exome AF: 0.0000382

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1433770 Hom.: 0 Cov.: 42 AF XY: 0.00000141 AC XY: 1 AN XY: 710600

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: 0.0000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000838 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	.;T;T;.;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.074
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.56	D;D;D;D;D
MetaSVM	Uncertain	0.38	D
MutationAssessor	Benign	1.8	.;L;.;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.1	N;N;N;.;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.016	D;D;D;.;T
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		1.0	.;D;.;.;.
Vest4		0.65
MutPred		0.25		.;Gain of catalytic residue at P2392 (P = 0.0159);.;.;.;
MVP		0.72
MPC		0.98
ClinPred		0.74	D
GERP RS		3.8
Varity_R		0.35
gMVP		0.64

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: rs55971316; hg19: chr9-139902962;