rs17222723

Positions:

chr10-99836239-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000392.5(ABCC2):c.3563T>A(p.Val1188Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0532 in 1,613,986 control chromosomes in the GnomAD database, including 2,596 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 249 hom., cov: 32)

Exomes 𝑓: 0.053 ( 2347 hom. )

Consequence

ABCC2
NM_000392.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.72

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002881676).

BP6

Variant 10-99836239-T-A is Benign according to our data. Variant chr10-99836239-T-A is described in ClinVar as [Benign]. Clinvar id is 298467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ABCC2	NM_000392.5 linkuse as main transcript	c.3563T>A	p.Val1188Glu	missense_variant	25/32	ENST00000647814.1	NP_000383.2
ABCC2	XM_006717630.4 linkuse as main transcript	c.2867T>A	p.Val956Glu	missense_variant	20/27		XP_006717693.1
ABCC2	XM_047424598.1 linkuse as main transcript	c.3563T>A	p.Val1188Glu	missense_variant	25/26		XP_047280554.1
ABCC2	XR_945604.4 linkuse as main transcript	n.3768T>A		non_coding_transcript_exon_variant	25/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1 linkuse as main transcript	c.3563T>A	p.Val1188Glu	missense_variant	25/32		NM_000392.5	ENSP00000497274	P1

Frequencies

GnomAD3 genomes

AF:

0.0539

AC:

8202

AN:

152062

Hom.:

245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0594

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0579

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.0225

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.0568

Gnomad OTH

AF:

0.0709

GnomAD3 exomes

AF:

0.0453

AC:

11386

AN:

251494

Hom.:

386

AF XY:

0.0457

AC XY:

6213

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0585

Gnomad AMR exome

AF:

0.0360

Gnomad ASJ exome

AF:

0.128

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.0182

Gnomad FIN exome

AF:

0.0225

Gnomad NFE exome

AF:

0.0568

Gnomad OTH exome

AF:

0.0611

GnomAD4 exome

AF:

0.0531

AC:

77680

AN:

1461806

Hom.:

2347

Cov.:

AF XY:

0.0525

AC XY:

38200

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0607

Gnomad4 AMR exome

AF:

0.0390

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0186

Gnomad4 FIN exome

AF:

0.0232

Gnomad4 NFE exome

AF:

0.0569

Gnomad4 OTH exome

AF:

0.0602

GnomAD4 genome

AF:

0.0540

AC:

8223

AN:

152180

Hom.:

249

Cov.:

AF XY:

0.0523

AC XY:

3891

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0599

Gnomad4 AMR

AF:

0.0579

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0205

Gnomad4 FIN

AF:

0.0225

Gnomad4 NFE

AF:

0.0567

Gnomad4 OTH

AF:

0.0707

Alfa

AF:

0.0604

Hom.:

260

Bravo

AF:

0.0586

TwinsUK

AF:

0.0607

AC:

225

ALSPAC

AF:

0.0555

AC:

214

ESP6500AA

AF:

0.0595

AC:

262

ESP6500EA

AF:

0.0617

AC:

531

ExAC

AF:

0.0430

AC:

5221

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0661

EpiControl

AF:

0.0727

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	This variant is associated with the following publications: (PMID: 25087612, 18926681, 16628674) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

ABCC2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 06, 2024

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

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

0.072

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.0030

DANN

Benign

0.17

DEOGEN2

Benign

0.088

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.19

.;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

-0.52

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

0.71

.;N

REVEL

Benign

0.21

Sift

Benign

0.97

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.0

B;B

Vest4

0.097

MPC

0.051

ClinPred

0.0029

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.089

gMVP

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over