2-214953891-G-C

Variant names:

• chr2-214953891-G-C
• rs137853289
• NM_173076.3:c.6610C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173076.3(ABCA12):​c.6610C>G​(p.Arg2204Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R2204Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCA12 NM_173076.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40
• Publications: 0 publications found

Genes affected

ABCA12 (HGNC:14637): (ATP binding cassette subfamily A member 12) 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, and White). This encoded protein is a member of the ABC1 subfamily, which is the only major ABC subfamily found exclusively in multicellular eukaryotes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

SNHG31 (HGNC:54196): (small nucleolar RNA host gene 31)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.886

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA12	NM_173076.3	c.6610C>G	p.Arg2204Gly	missense_variant	Exon 44 of 53	ENST00000272895.12	NP_775099.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12	c.6610C>G	p.Arg2204Gly	missense_variant	Exon 44 of 53	1	NM_173076.3	ENSP00000272895.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	D;.
Eigen	Benign	0.019
Eigen_PC	Benign	-0.079
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Uncertain	0.67	D
MutationAssessor	Uncertain	2.7	M;.
PhyloP100		3.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.023	D;T
Polyphen		1.0	D;D
Vest4		0.92
MutPred		0.65		Loss of helix (P = 0.0167);.;
MVP		0.87
MPC		0.84
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.31
gMVP		0.82
Mutation Taster		=48/52	disease causing

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: rs137853289; hg19: chr2-215818615;