10-99844450-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000392.5(ABCC2):c.3972C>T(p.Ile1324Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,613,504 control chromosomes in the GnomAD database, including 105,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8466 hom., cov: 33)

Exomes 𝑓: 0.36 ( 96644 hom. )

Consequence

ABCC2
NM_000392.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0690

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 10-99844450-C-T is Benign according to our data. Variant chr10-99844450-C-T is described in ClinVar as [Benign]. Clinvar id is 196101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-99844450-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.069 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC2	NM_000392.5 link	c.3972C>T	p.Ile1324Ile	synonymous_variant	Exon 28 of 32	ENST00000647814.1	NP_000383.2	Q92887
ABCC2	XM_006717630.4 link	c.3276C>T	p.Ile1092Ile	synonymous_variant	Exon 23 of 27		XP_006717693.1
ABCC2	XR_945604.4 link	n.4177C>T		non_coding_transcript_exon_variant	Exon 28 of 30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1 link	c.3972C>T	p.Ile1324Ile	synonymous_variant	Exon 28 of 32		NM_000392.5	ENSP00000497274.1		Q92887
ABCC2	ENST00000649459.1 link	n.320C>T		non_coding_transcript_exon_variant	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49678

AN:

152002

Hom.:

8473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.335

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.346

GnomAD3 exomes

AF:

0.341

AC:

85500

AN:

250980

Hom.:

14799

AF XY:

0.343

AC XY:

46531

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.349

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.232

Gnomad SAS exome

AF:

0.325

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.371

Gnomad OTH exome

AF:

0.358

GnomAD4 exome

AF:

0.361

AC:

528097

AN:

1461384

Hom.:

96644

Cov.:

AF XY:

0.361

AC XY:

262439

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.255

Gnomad4 AMR exome

AF:

0.348

Gnomad4 ASJ exome

AF:

0.347

Gnomad4 EAS exome

AF:

0.228

Gnomad4 SAS exome

AF:

0.328

Gnomad4 FIN exome

AF:

0.342

Gnomad4 NFE exome

AF:

0.374

Gnomad4 OTH exome

AF:

0.352

GnomAD4 genome

AF:

0.327

AC:

49695

AN:

152120

Hom.:

8466

Cov.:

AF XY:

0.326

AC XY:

24231

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.260

Gnomad4 AMR

AF:

0.344

Gnomad4 ASJ

AF:

0.351

Gnomad4 EAS

AF:

0.229

Gnomad4 SAS

AF:

0.322

Gnomad4 FIN

AF:

0.335

Gnomad4 NFE

AF:

0.366

Gnomad4 OTH

AF:

0.346

Alfa

AF:

0.332

Hom.:

4582

Bravo

AF:

0.323

Asia WGS

AF:

0.272

AC:

947

AN:

3478

EpiCase

AF:

0.367

EpiControl

AF:

0.372

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 17997497, 24743544, 21541183, 25087612) -

Dubin-Johnson syndrome

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

not specified

Benign:1

Dec 12, 2014

Eurofins Ntd Llc (ga)

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.2

DANN

Benign

0.67

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