rs2002042

chr10-99828174-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000392.5(ABCC2):c.2621-2133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 150,810 control chromosomes in the GnomAD database, including 5,612 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5612 hom., cov: 27)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC2	NM_000392.5	c.2621-2133C>T		intron_variant		ENST00000647814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC2	ENST00000647814.1	c.2621-2133C>T		intron_variant			NM_000392.5	P1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40272 AN: 150690 Hom.: 5615 Cov.: 27

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.267 AC: 40284 AN: 150810 Hom.: 5612 Cov.: 27 AF XY: 0.273 AC XY: 20080 AN XY: 73600

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.238

Alfa AF: 0.253 Hom.: 10195

Bravo AF: 0.263

Asia WGS AF: 0.277 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.50
Dann	Benign	0.34

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

Other links and lift over

dbSNP: rs2002042; hg19: chr10-101587931;