10-99782847-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2

The NM_000392.5(ABCC2):​c.3G>T​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ABCC2
NM_000392.5 start_lost

Scores

3
5
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02
Variant links:
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 3 ACMG points.

PVS1
Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 696 CDS bases. Genomic position: 99797160. Lost 0.150 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCC2NM_000392.5 linkc.3G>T p.Met1? start_lost Exon 1 of 32 ENST00000647814.1 NP_000383.2 Q92887

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCC2ENST00000647814.1 linkc.3G>T p.Met1? start_lost Exon 1 of 32 NM_000392.5 ENSP00000497274.1 Q92887

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251334
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135836
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461754
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.21
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.068
.;T;T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.12
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.90
.;.;D
M_CAP
Uncertain
0.20
D
MetaRNN
Pathogenic
0.97
D;D;D
MetaSVM
Uncertain
-0.18
T
PROVEAN
Benign
-0.32
.;.;N
REVEL
Benign
0.18
Sift
Benign
0.039
.;.;D
Sift4G
Benign
0.23
.;.;T
Polyphen
0.077
.;B;B
Vest4
0.66
MutPred
0.96
Gain of catalytic residue at M1 (P = 0.0621);Gain of catalytic residue at M1 (P = 0.0621);Gain of catalytic residue at M1 (P = 0.0621);
MVP
0.77
ClinPred
0.97
D
GERP RS
3.7
Varity_R
0.51
gMVP
0.31

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1309534430; hg19: chr10-101542604; API