chr2-219209955-G-C

Variant names:

• chr2-219209955-G-C
• rs372899405
• NM_005689.4:c.2512C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005689.4(ABCB6):​c.2512C>G​(p.Gln838Glu) 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 benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCB6 NM_005689.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05087492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB6	NM_005689.4	c.2512C>G	p.Gln838Glu	missense_variant	Exon 19 of 19	ENST00000265316.9	NP_005680.1
ABCB6	NM_001349828.2	c.2374C>G	p.Gln792Glu	missense_variant	Exon 18 of 18		NP_001336757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB6	ENST00000265316.9	c.2512C>G	p.Gln838Glu	missense_variant	Exon 19 of 19	1	NM_005689.4	ENSP00000265316.3
ENSG00000284820	ENST00000446716.5	n.*4296C>G		non_coding_transcript_exon_variant	Exon 22 of 22	2		ENSP00000398528.1
ENSG00000284820	ENST00000446716.5	n.*4296C>G		3_prime_UTR_variant	Exon 22 of 22	2		ENSP00000398528.1

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	Benign	0.062
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.10
DANN	Benign	0.63
DEOGEN2	Benign	0.041	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-0.055	N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.46	N;.
REVEL	Benign	0.18
Sift	Benign	0.76	T;.
Sift4G	Benign	1.0	T;.
Polyphen		0.0	B;B
Vest4		0.051
MutPred		0.21		Loss of methylation at K836 (P = 0.1046);.;
MVP		0.71
MPC		0.23
ClinPred		0.050	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.25

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: rs372899405; hg19: chr2-220074677; COSMIC: COSV54699398; COSMIC: COSV54699398;