10-99852563-C-T

Variant names:

• chr10-99852563-C-T
• rs12826
• NM_000392.5:c.*932C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000392.5(ABCC2):​c.*932C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,048 control chromosomes in the GnomAD database, including 7,962 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 0.31 (7962 hom., cov: 33)
• Consequence: ABCC2 NM_000392.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520
• 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: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC2	NM_000392.5	c.*932C>T		3_prime_UTR_variant	Exon 32 of 32	ENST00000647814.1	NP_000383.2
ABCC2	XM_006717630.4	c.*932C>T		3_prime_UTR_variant	Exon 27 of 27		XP_006717693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1	c.*932C>T		3_prime_UTR_variant	Exon 32 of 32		NM_000392.5	ENSP00000497274.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47177 AN: 151930 Hom.: 7968 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.310 AC: 47187 AN: 152048 Hom.: 7962 Cov.: 33 AF XY: 0.310 AC XY: 23055 AN XY: 74310

African (AFR) AF: 0.187 AC: 7768 AN: 41454

American (AMR) AF: 0.343 AC: 5243 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1234 AN: 3468

East Asian (EAS) AF: 0.230 AC: 1189 AN: 5180

South Asian (SAS) AF: 0.323 AC: 1557 AN: 4822

European-Finnish (FIN) AF: 0.338 AC: 3563 AN: 10544

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25360 AN: 67996

Other (OTH) AF: 0.337 AC: 712 AN: 2110

Alfa AF: 0.348 Hom.: 17684

Bravo AF: 0.304

Asia WGS AF: 0.266 AC: 927 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	1.0
DANN	Benign	0.76
PhyloP100		-0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12826; hg19: chr10-101612320;