NM_000392.5:c.207+2504C>T

Variant names:

• chr10-99787285-C-T
• rs2756105
• NM_000392.5:c.207+2504C>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.207+2504C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,080 control chromosomes in the GnomAD database, including 11,190 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 0.38 (11190 hom., cov: 34)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC2	NM_000392.5	c.207+2504C>T		intron_variant	Intron 2 of 31	ENST00000647814.1	NP_000383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1	c.207+2504C>T		intron_variant	Intron 2 of 31		NM_000392.5	ENSP00000497274.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57043 AN: 151962 Hom.: 11186 Cov.: 34

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.375 AC: 57062 AN: 152080 Hom.: 11190 Cov.: 34 AF XY: 0.373 AC XY: 27713 AN XY: 74330

African (AFR) AF: 0.283 AC: 11756 AN: 41468

American (AMR) AF: 0.412 AC: 6295 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3466

East Asian (EAS) AF: 0.230 AC: 1189 AN: 5170

South Asian (SAS) AF: 0.376 AC: 1810 AN: 4818

European-Finnish (FIN) AF: 0.364 AC: 3845 AN: 10560

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29025 AN: 67982

Other (OTH) AF: 0.421 AC: 889 AN: 2114

Alfa AF: 0.416 Hom.: 20434

Bravo AF: 0.373

Asia WGS AF: 0.329 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.1
DANN	Benign	0.73
PhyloP100		-0.24
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: rs2756105; hg19: chr10-101547042;