rs717620

Variant names:

• chr10-99782821-C-T
• rs717620
• NM_000392.5:c.-24C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-99782821-C-T
• chr10-99782821-C-A
• chr10-99782821-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000392.5(ABCC2):​c.-24C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,610,598 control chromosomes in the GnomAD database, including 29,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2125 hom., cov: 33)
  • Exomes 𝑓: 0.19 (27698 hom.)
• Consequence: ABCC2 NM_000392.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.07
• Publications: 440 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-99782821-C-T is Benign according to our data. Variant chr10-99782821-C-T is described in ClinVar as Benign. ClinVar VariationId is 298437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000392.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC2	NM_000392.5	MANE Select	c.-24C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 32	NP_000383.2	Q92887
	ABCC2	NM_000392.5	MANE Select	c.-24C>T		5_prime_UTR	Exon 1 of 32	NP_000383.2	Q92887

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC2	ENST00000647814.1	MANE Select	c.-24C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 32	ENSP00000497274.1	Q92887
	ABCC2	ENST00000647814.1	MANE Select	c.-24C>T		5_prime_UTR	Exon 1 of 32	ENSP00000497274.1	Q92887
	ABCC2	ENST00000648689.1		c.-24C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000496972.1	A0A3B3IRZ2

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23555 AN: 152080 Hom.: 2127 Cov.: 33

Gnomad AFR AF: 0.0618

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.148

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.178

GnomAD2 exomes AF: 0.171 AC: 42814 AN: 251040 AF XY: 0.171

Gnomad AFR exome AF: 0.0565

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.213

Gnomad FIN exome AF: 0.195

Gnomad NFE exome AF: 0.200

Gnomad OTH exome AF: 0.183

GnomAD4 exome AF: 0.190 AC: 276603 AN: 1458400 Hom.: 27698 Cov.: 31 AF XY: 0.188 AC XY: 136569 AN XY: 725676

African (AFR) AF: 0.0536 AC: 1794 AN: 33462

American (AMR) AF: 0.132 AC: 5906 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 5243 AN: 26108

East Asian (EAS) AF: 0.205 AC: 8120 AN: 39654

South Asian (SAS) AF: 0.112 AC: 9671 AN: 86192

European-Finnish (FIN) AF: 0.194 AC: 10346 AN: 53312

Middle Eastern (MID) AF: 0.132 AC: 760 AN: 5764

European-Non Finnish (NFE) AF: 0.202 AC: 223758 AN: 1108902

Other (OTH) AF: 0.183 AC: 11005 AN: 60296

GnomAD4 genome AF: 0.155 AC: 23547 AN: 152198 Hom.: 2125 Cov.: 33 AF XY: 0.156 AC XY: 11601 AN XY: 74402

African (AFR) AF: 0.0617 AC: 2562 AN: 41556

American (AMR) AF: 0.163 AC: 2494 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 730 AN: 3466

East Asian (EAS) AF: 0.206 AC: 1069 AN: 5180

South Asian (SAS) AF: 0.117 AC: 563 AN: 4830

European-Finnish (FIN) AF: 0.190 AC: 2009 AN: 10590

Middle Eastern (MID) AF: 0.142 AC: 41 AN: 288

European-Non Finnish (NFE) AF: 0.199 AC: 13495 AN: 67984

Other (OTH) AF: 0.179 AC: 377 AN: 2106

Alfa AF: 0.183 Hom.: 11582

Bravo AF: 0.147

Asia WGS AF: 0.154 AC: 533 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ABCC2-related disorder (1)
-	-	1	Dubin-Johnson syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.49
PhyloP100		1.1
PromoterAI		-0.038	Neutral
Mutation Taster		=298/2	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: rs717620; hg19: chr10-101542578; COSMIC: COSV64970575;