dbSNP rs11597282: ABCC2:c.2621-44G>A (chr10-99830263-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000392.5(ABCC2):c.2621-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,613,100 control chromosomes in the GnomAD database, including 943 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 0.024 ( 55 hom., cov: 32)

Exomes 𝑓: 0.032 ( 888 hom. )

Consequence

ABCC2
NM_000392.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.445

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

Dubin-Johnson syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ABCC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0242 (3678/152108) while in subpopulation NFE AF = 0.0354 (2408/67994). AF 95% confidence interval is 0.0342. There are 55 homozygotes in GnomAd4. There are 1781 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC2	NM_000392.5 link	c.2621-44G>A		intron_variant	Intron 19 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.2621-44G>A		intron_variant	Intron 19 of 31		NM_000392.5	ENSP00000497274.1		Q92887

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3683

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00580

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.0354

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0290

Gnomad NFE

AF:

0.0354

Gnomad OTH

AF:

0.0312

GnomAD2 exomes

AF:

0.0255

AC:

6413

AN:

251284

AF XY:

0.0258

show subpopulations

Gnomad AFR exome

AF:

0.00560

Gnomad AMR exome

AF:

0.0267

Gnomad ASJ exome

AF:

0.0294

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0139

Gnomad NFE exome

AF:

0.0366

Gnomad OTH exome

AF:

0.0284

GnomAD4 exome

AF:

0.0315

AC:

46042

AN:

1460992

Hom.:

888

Cov.:

AF XY:

0.0312

AC XY:

22660

AN XY:

726872

show subpopulations

African (AFR)

AF:

0.00454

AC:

152

AN:

33462

American (AMR)

AF:

0.0280

AC:

1253

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0322

AC:

841

AN:

26124

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39690

South Asian (SAS)

AF:

0.0153

AC:

1317

AN:

86218

European-Finnish (FIN)

AF:

0.0140

AC:

745

AN:

53348

Middle Eastern (MID)

AF:

0.0251

AC:

143

AN:

5694

European-Non Finnish (NFE)

AF:

0.0359

AC:

39940

AN:

1111388

Other (OTH)

AF:

0.0273

AC:

1649

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

2085

4170

6256

8341

10426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1480

2960

4440

5920

7400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0242

AC:

3678

AN:

152108

Hom.:

Cov.:

AF XY:

0.0240

AC XY:

1781

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.00579

AC:

240

AN:

41482

American (AMR)

AF:

0.0353

AC:

540

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0329

AC:

114

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.0162

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0132

AC:

140

AN:

10610

Middle Eastern (MID)

AF:

0.0243

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0354

AC:

2408

AN:

67994

Other (OTH)

AF:

0.0304

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

182

365

547

730

912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0306

Hom.:

171

Bravo

AF:

0.0251

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.10

(source)

DANN

Benign

0.40

PhyloP100

-0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over