chr2-219210394-C-A

Variant names:

• chr2-219210394-C-A
• rs201104967
• NM_005689.4:c.2338G>T

Variant summary

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

The NM_005689.4(ABCB6):​c.2338G>T​(p.Val780Leu) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V780I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCB6 NM_005689.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19

Genes affected

ABCB6 (HGNC:47): (ATP binding cassette subfamily B member 6 (LAN blood group)) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. ABC proteins transport various molecules across extra- and intra-cellular membranes. This protein is a member of the heavy metal importer subfamily and plays a role in porphyrin transport. This gene is the molecular basis of the Langereis (Lan) blood group antigen and mutations in this gene underlie familial pseudohyperkalemia and dyschromatosis universalis hereditaria. [provided by RefSeq, Mar 2017]

ENSG00000284820 (HGNC:):

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
ABCB6	NM_005689.4	c.2338G>T	p.Val780Leu	missense_variant	Exon 17 of 19	ENST00000265316.9	NP_005680.1
ABCB6	NM_001349828.2	c.2200G>T	p.Val734Leu	missense_variant	Exon 16 of 18		NP_001336757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB6	ENST00000265316.9	c.2338G>T	p.Val780Leu	missense_variant	Exon 17 of 19	1	NM_005689.4	ENSP00000265316.3
ENSG00000284820	ENST00000446716.5	n.*4122G>T		non_coding_transcript_exon_variant	Exon 20 of 22	2		ENSP00000398528.1
ENSG00000284820	ENST00000446716.5	n.*4122G>T		3_prime_UTR_variant	Exon 20 of 22	2		ENSP00000398528.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.97	D;D
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Uncertain	0.047	D
MutationAssessor	Benign	0.41	N;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.1	N;.
REVEL	Uncertain	0.51
Sift	Uncertain	0.011	D;.
Sift4G	Uncertain	0.019	D;.
Polyphen		0.97	D;D
Vest4		0.69
MutPred		0.47		Loss of catalytic residue at V780 (P = 0.0763);.;
MVP		0.98
MPC		0.33
ClinPred		0.81	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.49
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs201104967; hg19: chr2-220075116;