rs8187710

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000392.5(ABCC2):c.4544G>A(p.Cys1515Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 1,613,856 control chromosomes in the GnomAD database, including 3,546 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. C1515C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.083 ( 719 hom., cov: 33)

Exomes 𝑓: 0.056 ( 2827 hom. )

Consequence

ABCC2
NM_000392.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.301

Publications

152 publications found

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]

ABCC2 Gene-Disease associations (from GenCC):

Dubin-Johnson syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ABCC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022177398).

BP6

Variant 10-99851537-G-A is Benign according to our data. Variant chr10-99851537-G-A is described in ClinVar as Benign. ClinVar VariationId is 298481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC2	NM_000392.5 link	c.4544G>A	p.Cys1515Tyr	missense_variant	Exon 32 of 32	ENST00000647814.1	NP_000383.2	Q92887
ABCC2	XM_006717630.4 link	c.3848G>A	p.Cys1283Tyr	missense_variant	Exon 27 of 27		XP_006717693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC2	ENST00000647814.1 link	c.4544G>A	p.Cys1515Tyr	missense_variant	Exon 32 of 32	NM_000392.5	ENSP00000497274.1	Q92887
ABCC2	ENST00000648523.1 link	n.*385G>A		non_coding_transcript_exon_variant	Exon 5 of 5		ENSP00000497778.1	A0A3B3ITG8
ABCC2	ENST00000648523.1 link	n.*385G>A		3_prime_UTR_variant	Exon 5 of 5		ENSP00000497778.1	A0A3B3ITG8

Frequencies

GnomAD3 genomes

AF:

0.0825

AC:

12539

AN:

152076

Hom.:

709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0704

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0203

Gnomad FIN

AF:

0.0225

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.0572

Gnomad OTH

AF:

0.0903

GnomAD2 exomes

AF:

0.0528

AC:

13264

AN:

251416

AF XY:

0.0507

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.0414

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.000707

Gnomad FIN exome

AF:

0.0225

Gnomad NFE exome

AF:

0.0572

Gnomad OTH exome

AF:

0.0658

GnomAD4 exome

AF:

0.0560

AC:

81918

AN:

1461662

Hom.:

2827

Cov.:

AF XY:

0.0549

AC XY:

39955

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.163

AC:

5446

AN:

33456

American (AMR)

AF:

0.0451

AC:

2015

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

3439

AN:

26124

East Asian (EAS)

AF:

0.000302

AC:

AN:

39694

South Asian (SAS)

AF:

0.0188

AC:

1623

AN:

86256

European-Finnish (FIN)

AF:

0.0233

AC:

1243

AN:

53418

Middle Eastern (MID)

AF:

0.131

AC:

758

AN:

5768

European-Non Finnish (NFE)

AF:

0.0569

AC:

63317

AN:

1111844

Other (OTH)

AF:

0.0673

AC:

4065

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

3916

7832

11748

15664

19580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2430

4860

7290

9720

12150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0826

AC:

12578

AN:

152194

Hom.:

719

Cov.:

AF XY:

0.0793

AC XY:

5899

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.158

AC:

6573

AN:

41476

American (AMR)

AF:

0.0703

AC:

1075

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

425

AN:

3470

East Asian (EAS)

AF:

0.000771

AC:

AN:

5186

South Asian (SAS)

AF:

0.0207

AC:

100

AN:

4830

European-Finnish (FIN)

AF:

0.0225

AC:

238

AN:

10600

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0572

AC:

3890

AN:

68022

Other (OTH)

AF:

0.0899

AC:

190

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

555

1110

1665

2220

2775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0662

Hom.:

2127

Bravo

AF:

0.0916

TwinsUK

AF:

0.0615

AC:

228

ALSPAC

AF:

0.0558

AC:

215

ESP6500AA

AF:

0.157

AC:

692

ESP6500EA

AF:

0.0620

AC:

533

ExAC

AF:

0.0524

AC:

6359

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0665

EpiControl

AF:

0.0734

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25087612, 18926681, 22027652) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ABCC2-related disorder

Benign:1

Mar 06, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Dubin-Johnson syndrome

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.3

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.062

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.67

.;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.48

N;N

PhyloP100

0.30

PrimateAI

Uncertain

0.52

PROVEAN

Benign

4.1

.;N

REVEL

Benign

0.11

Sift

Benign

0.63

.;T

Sift4G

Benign

0.25

.;T

Polyphen

0.0

B;B

Vest4

0.018

MPC

0.052

ClinPred

0.0051

GERP RS

2.0

Varity_R

0.084

gMVP

0.41

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over