10-99806422-A-G

Variant names:

• chr10-99806422-A-G
• rs2756112
• NM_000392.5:c.1531-962A>G

Variant summary

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

The NM_000392.5(ABCC2):​c.1531-962A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 152,244 control chromosomes in the GnomAD database, including 69,446 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 0.95 (69446 hom., cov: 30)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC2	NM_000392.5	c.1531-962A>G		intron_variant	Intron 11 of 31	ENST00000647814.1	NP_000383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1	c.1531-962A>G		intron_variant	Intron 11 of 31		NM_000392.5	ENSP00000497274.1

Frequencies

GnomAD3 genomes AF: 0.955 AC: 145273 AN: 152126 Hom.: 69387 Cov.: 30

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.834

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.932

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

GnomAD4 genome AF: 0.955 AC: 145391 AN: 152244 Hom.: 69446 Cov.: 30 AF XY: 0.958 AC XY: 71268 AN XY: 74422

African (AFR) AF: 0.953 AC: 39592 AN: 41532

American (AMR) AF: 0.948 AC: 14488 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3108 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5172 AN: 5174

South Asian (SAS) AF: 0.989 AC: 4772 AN: 4826

European-Finnish (FIN) AF: 0.987 AC: 10475 AN: 10608

Middle Eastern (MID) AF: 0.832 AC: 243 AN: 292

European-Non Finnish (NFE) AF: 0.951 AC: 64685 AN: 68032

Other (OTH) AF: 0.932 AC: 1969 AN: 2112

Alfa AF: 0.947 Hom.: 77930

Bravo AF: 0.951

Asia WGS AF: 0.989 AC: 3440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.78
PhyloP100		-0.21
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: rs2756112; hg19: chr10-101566179;