dbSNP rs2073337: ABCC2:c.1668+148A>G (chr10-99807669-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.806

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 ClinVar 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 link	c.1668+148A>G		intron_variant	Intron 12 of 31	ENST00000647814.1	NP_000383.2	Q92887

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1 link	c.1668+148A>G		intron_variant	Intron 12 of 31		NM_000392.5	ENSP00000497274.1		Q92887

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60165

AN:

151960

Hom.:

12113

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.431

Gnomad4 AMR exome

AF:

0.370

Gnomad4 ASJ exome

AF:

0.402

Gnomad4 EAS exome

AF:

0.226

Gnomad4 SAS exome

AF:

0.382

Gnomad4 FIN exome

AF:

0.363

Gnomad4 NFE exome

AF:

0.385

Gnomad4 OTH exome

AF:

0.381

GnomAD4 genome

AF:

0.396

AC:

60241

AN:

152078

Hom.:

12136

Cov.:

AF XY:

0.394

AC XY:

29299

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.440

Gnomad4 AMR

AF:

0.387

Gnomad4 ASJ

AF:

0.416

Gnomad4 EAS

AF:

0.232

Gnomad4 SAS

AF:

0.387

Gnomad4 FIN

AF:

0.357

Gnomad4 NFE

AF:

0.388

Gnomad4 OTH

AF:

0.399

Alfa

AF:

0.385

Hom.:

14331

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

LINK: link

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over