NM_001606.5:c.7117G>C

Variant names:

• chr9-137008574-C-G
• rs1477124853
• NM_001606.5:c.7117G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001606.5(ABCA2):​c.7117G>C​(p.Glu2373Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. E2373K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCA2 NM_001606.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.89
• 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3612546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA2	NM_001606.5	c.7117G>C	p.Glu2373Gln	missense_variant	Exon 48 of 49	ENST00000341511.11	NP_001597.2
ABCA2	NM_212533.3	c.7207G>C	p.Glu2403Gln	missense_variant	Exon 48 of 49		NP_997698.1
ABCA2	NM_001411042.1	c.7114G>C	p.Glu2372Gln	missense_variant	Exon 47 of 48		NP_001397971.1
ABCA2	XM_047422921.1	c.7204G>C	p.Glu2402Gln	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.7117G>C	p.Glu2373Gln	missense_variant	Exon 48 of 49	5	NM_001606.5	ENSP00000344155.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.29	.;T;T;.;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;D;D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.36	T;T;T;T;T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	1.2	.;L;.;.;.
PhyloP100		5.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.48	N;N;N;.;N
REVEL	Uncertain	0.35
Sift	Benign	0.052	T;T;D;.;T
Sift4G	Benign	0.46	T;T;T;T;T
Polyphen		0.89	.;P;.;.;.
Vest4		0.40
MutPred		0.20		.;Gain of loop (P = 0.0312);.;.;.;
MVP		0.60
MPC		1.7
ClinPred		0.90	D
GERP RS		4.2
Varity_R		0.18
gMVP		0.24
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs1477124853; hg19: chr9-139903026;