rs2804398

Variant names:

• chr10-99798877-A-T
• rs2804398
• NM_000392.5:c.868-330A>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.868-330A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,000 control chromosomes in the GnomAD database, including 8,955 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 0.34 (8955 hom., cov: 32)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.990
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC2	NM_000392.5	c.868-330A>T		intron_variant	Intron 7 of 31	ENST00000647814.1	NP_000383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1	c.868-330A>T		intron_variant	Intron 7 of 31		NM_000392.5	ENSP00000497274.1
ABCC2	ENST00000648324.1	n.*705-334A>T		intron_variant	Intron 8 of 8			ENSP00000497248.1
ABCC2	ENST00000649493.1	n.*683-330A>T		intron_variant	Intron 8 of 8			ENSP00000496847.1
ABCC2	ENST00000649932.1	n.*390-330A>T		intron_variant	Intron 7 of 7			ENSP00000498120.1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51230 AN: 151882 Hom.: 8950 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.337 AC: 51262 AN: 152000 Hom.: 8955 Cov.: 32 AF XY: 0.337 AC XY: 25008 AN XY: 74282

African (AFR) AF: 0.272 AC: 11258 AN: 41450

American (AMR) AF: 0.363 AC: 5539 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1275 AN: 3468

East Asian (EAS) AF: 0.142 AC: 735 AN: 5166

South Asian (SAS) AF: 0.357 AC: 1722 AN: 4818

European-Finnish (FIN) AF: 0.352 AC: 3713 AN: 10558

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25715 AN: 67964

Other (OTH) AF: 0.359 AC: 756 AN: 2108

Alfa AF: 0.358 Hom.: 1453

Bravo AF: 0.332

Asia WGS AF: 0.287 AC: 999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.4
DANN	Benign	0.72
PhyloP100		0.99
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: rs2804398; hg19: chr10-101558634; COSMIC: COSV64970628; COSMIC: COSV64970628;