rs2073337

Variant names:

• chr10-99807669-A-G
• rs2073337
• NM_000392.5:c.1668+148A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-99807669-A-G
• chr10-99807669-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000392.5(ABCC2):​c.1668+148A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,142,614 control chromosomes in the GnomAD database, including 85,634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (12136 hom., cov: 32)
  • Exomes 𝑓: 0.38 (73498 hom.)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.806
• Publications: 10 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-99807669-A-G is Benign according to our data. Variant chr10-99807669-A-G is described in CliVar as Benign. Clinvar id is 1289402.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-99807669-A-G is described in CliVar as Benign. Clinvar id is 1289402.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC2	NM_000392.5	c.1668+148A>G		intron_variant	Intron 12 of 31	ENST00000647814.1	NP_000383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1	c.1668+148A>G		intron_variant	Intron 12 of 31		NM_000392.5	ENSP00000497274.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60165 AN: 151960 Hom.: 12113 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.379 AC: 375309 AN: 990536 Hom.: 73498 AF XY: 0.380 AC XY: 192594 AN XY: 507084

African (AFR) AF: 0.431 AC: 10232 AN: 23740

American (AMR) AF: 0.370 AC: 13393 AN: 36150

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 8992 AN: 22386

East Asian (EAS) AF: 0.226 AC: 7888 AN: 34938

South Asian (SAS) AF: 0.382 AC: 27669 AN: 72390

European-Finnish (FIN) AF: 0.363 AC: 15686 AN: 43156

Middle Eastern (MID) AF: 0.362 AC: 1169 AN: 3226

European-Non Finnish (NFE) AF: 0.385 AC: 273298 AN: 709978

Other (OTH) AF: 0.381 AC: 16982 AN: 44572

GnomAD4 genome AF: 0.396 AC: 60241 AN: 152078 Hom.: 12136 Cov.: 32 AF XY: 0.394 AC XY: 29299 AN XY: 74340

African (AFR) AF: 0.440 AC: 18244 AN: 41490

American (AMR) AF: 0.387 AC: 5926 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1442 AN: 3468

East Asian (EAS) AF: 0.232 AC: 1196 AN: 5162

South Asian (SAS) AF: 0.387 AC: 1866 AN: 4824

European-Finnish (FIN) AF: 0.357 AC: 3769 AN: 10562

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.388 AC: 26386 AN: 67966

Other (OTH) AF: 0.399 AC: 841 AN: 2106

Alfa AF: 0.387 Hom.: 18553

Bravo AF: 0.397

Asia WGS AF: 0.343 AC: 1194 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.056
DANN	Benign	0.32
PhyloP100		-0.81
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: rs2073337; hg19: chr10-101567426;