rs8187692
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000392.5(ABCC2):c.3542G>A(p.Arg1181Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00041 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1181L) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00043 ( 0 hom. )
Consequence
ABCC2
NM_000392.5 missense
NM_000392.5 missense
Scores
2
7
5
Clinical Significance
Conservation
PhyloP100: 6.87
Genes affected
ABCC2 (HGNC:53): (ATP binding cassette subfamily C member 2) The 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 intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein is expressed in the canalicular (apical) part of the hepatocyte and functions in biliary transport. Substrates include anticancer drugs such as vinblastine; therefore, this protein appears to contribute to drug resistance in mammalian cells. Several different mutations in this gene have been observed in patients with Dubin-Johnson syndrome (DJS), an autosomal recessive disorder characterized by conjugated hyperbilirubinemia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC2 | NM_000392.5 | c.3542G>A | p.Arg1181Gln | missense_variant | 25/32 | ENST00000647814.1 | |
ABCC2 | XM_006717630.4 | c.2846G>A | p.Arg949Gln | missense_variant | 20/27 | ||
ABCC2 | XM_047424598.1 | c.3542G>A | p.Arg1181Gln | missense_variant | 25/26 | ||
ABCC2 | XR_945604.4 | n.3747G>A | non_coding_transcript_exon_variant | 25/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC2 | ENST00000647814.1 | c.3542G>A | p.Arg1181Gln | missense_variant | 25/32 | NM_000392.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000378 AC: 95AN: 251486Hom.: 0 AF XY: 0.000375 AC XY: 51AN XY: 135914
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GnomAD4 exome AF: 0.000430 AC: 629AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.000414 AC XY: 301AN XY: 727242
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GnomAD4 genome ? AF: 0.000210 AC: 32AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74320
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dubin-Johnson syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
P
PrimateAI
Benign
T
Polyphen
D;D
Vest4
0.50
MutPred
Gain of ubiquitination at K1184 (P = 0.0546);Gain of ubiquitination at K1184 (P = 0.0546);
MVP
0.94
MPC
0.29
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at