rs717620

Positions:

chr10-99782821-C-T

Variant summary

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

The NM_000392.5(ABCC2):c.-24C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,610,598 control chromosomes in the GnomAD database, including 29,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2125 hom., cov: 33)

Exomes 𝑓: 0.19 ( 27698 hom. )

Consequence

ABCC2
NM_000392.5 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.07

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 (BayesDel_noAF=-0.78).

BP6

Variant 10-99782821-C-T is Benign according to our data. Variant chr10-99782821-C-T is described in ClinVar as [Benign]. Clinvar id is 298437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC2	NM_000392.5 linkuse as main transcript	c.-24C>T		5_prime_UTR_variant	1/32	ENST00000647814.1	NP_000383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1 linkuse as main transcript	c.-24C>T		5_prime_UTR_variant	1/32		NM_000392.5	ENSP00000497274	P1

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23555

AN:

152080

Hom.:

2127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0618

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.148

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.171

AC:

42814

AN:

251040

Hom.:

3942

AF XY:

0.171

AC XY:

23245

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.0565

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.213

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.195

Gnomad NFE exome

AF:

0.200

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.190

AC:

276603

AN:

1458400

Hom.:

27698

Cov.:

AF XY:

0.188

AC XY:

136569

AN XY:

725676

show subpopulations

Gnomad4 AFR exome

AF:

0.0536

Gnomad4 AMR exome

AF:

0.132

Gnomad4 ASJ exome

AF:

0.201

Gnomad4 EAS exome

AF:

0.205

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.194

Gnomad4 NFE exome

AF:

0.202

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.155

AC:

23547

AN:

152198

Hom.:

2125

Cov.:

AF XY:

0.156

AC XY:

11601

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0617

Gnomad4 AMR

AF:

0.163

Gnomad4 ASJ

AF:

0.211

Gnomad4 EAS

AF:

0.206

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.199

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.191

Hom.:

6167

Bravo

AF:

0.147

Asia WGS

AF:

0.154

AC:

533

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	This variant is associated with the following publications: (PMID: 19415824, 22664480, 16788565, 24743544, 19890061, 21451505) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 18, 2017

- -

ABCC2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 22, 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

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.49

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