rs2756109

Variant names:

• chr10-99798989-G-T
• rs2756109
• NM_000392.5:c.868-218G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-99798989-G-T
• chr10-99798989-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000392.5(ABCC2):​c.868-218G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,924 control chromosomes in the GnomAD database, including 21,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.53 (21326 hom., cov: 31)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.604
• Publications: 16 publications found

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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 10-99798989-G-T is Benign according to our data. Variant chr10-99798989-G-T is described in ClinVar as Benign. ClinVar VariationId is 1233362.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000392.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC2	NM_000392.5	MANE Select	c.868-218G>T		intron	N/A	NP_000383.2	Q92887

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC2	ENST00000647814.1	MANE Select	c.868-218G>T		intron	N/A	ENSP00000497274.1	Q92887
	ABCC2	ENST00000648324.1		n.*705-222G>T		intron	N/A	ENSP00000497248.1	A0A3B3IS94
	ABCC2	ENST00000649493.1		n.*683-218G>T		intron	N/A	ENSP00000496847.1	A0A3B3IRU4

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79880 AN: 151806 Hom.: 21319 Cov.: 31

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.545

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.526 AC: 79915 AN: 151924 Hom.: 21326 Cov.: 31 AF XY: 0.523 AC XY: 38791 AN XY: 74232

African (AFR) AF: 0.473 AC: 19602 AN: 41408

American (AMR) AF: 0.517 AC: 7887 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1990 AN: 3472

East Asian (EAS) AF: 0.326 AC: 1682 AN: 5160

South Asian (SAS) AF: 0.626 AC: 3008 AN: 4806

European-Finnish (FIN) AF: 0.503 AC: 5298 AN: 10538

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38575 AN: 67958

Other (OTH) AF: 0.547 AC: 1157 AN: 2116

Alfa AF: 0.562 Hom.: 18350

Bravo AF: 0.522

Asia WGS AF: 0.481 AC: 1674 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.9
DANN	Benign	0.83
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2756109; hg19: chr10-101558746;