2-219213495-G-T

Position:

• chr2-219213495-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_005689.4(ABCB6):​c.1663C>A​(p.Gln555Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCB6 NM_005689.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.85

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.908
• PP5: Variant 2-219213495-G-T is Pathogenic according to our data. Variant chr2-219213495-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 208249.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB6	NM_005689.4	c.1663C>A	p.Gln555Lys	missense_variant	11/19	ENST00000265316.9	NP_005680.1
ABCB6	NM_001349828.2	c.1525C>A	p.Gln509Lys	missense_variant	10/18		NP_001336757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB6	ENST00000265316.9	c.1663C>A	p.Gln555Lys	missense_variant	11/19	1	NM_005689.4	ENSP00000265316.3
ENSG00000284820	ENST00000446716.5	n.*3622C>A		non_coding_transcript_exon_variant	15/22	2		ENSP00000398528.1
ENSG00000284820	ENST00000446716.5	n.*3622C>A		3_prime_UTR_variant	15/22	2		ENSP00000398528.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Dyschromatosis universalis hereditaria 3 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Pathogenic	0.50	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Benign	1.0	L;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.7	D;.
REVEL	Pathogenic	0.95
Sift	Benign	0.12	T;.
Sift4G	Benign	0.20	T;.
Polyphen		1.0	D;D
Vest4		0.95
MutPred		0.64		Gain of methylation at Q555 (P = 0.0121);.;
MVP		0.98
MPC		0.88
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.72
gMVP		0.96

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: rs796065353; hg19: chr2-220078217;