chr10-99808256-C-G

Variant names:

• chr10-99808256-C-G
• rs8187674
• NM_000392.5:c.1815+27C>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.1815+27C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00436 in 1,613,360 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (124 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (107 hom.)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0880
• Publications: 4 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=-0.92).
• BP6: Variant 10-99808256-C-G is Benign according to our data. Variant chr10-99808256-C-G is described in ClinVar as Benign. ClinVar VariationId is 1254550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0702 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.1815+27C>G		intron	N/A	NP_000383.2	Q92887

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC2	ENST00000647814.1	MANE Select	c.1815+27C>G		intron	N/A	ENSP00000497274.1	Q92887

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3218 AN: 152134 Hom.: 124 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00594 AC: 1492 AN: 250994 AF XY: 0.00463

Gnomad AFR exome AF: 0.0737

Gnomad AMR exome AF: 0.00451

Gnomad ASJ exome AF: 0.000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000978

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00260 AC: 3805 AN: 1461108 Hom.: 107 Cov.: 32 AF XY: 0.00231 AC XY: 1678 AN XY: 726912

African (AFR) AF: 0.0753 AC: 2520 AN: 33452

American (AMR) AF: 0.00517 AC: 231 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000536 AC: 14 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86254

European-Finnish (FIN) AF: 0.000113 AC: 6 AN: 53056

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5764

European-Non Finnish (NFE) AF: 0.000590 AC: 656 AN: 1111662

Other (OTH) AF: 0.00542 AC: 327 AN: 60382

GnomAD4 genome AF: 0.0212 AC: 3228 AN: 152252 Hom.: 124 Cov.: 32 AF XY: 0.0205 AC XY: 1524 AN XY: 74432

African (AFR) AF: 0.0724 AC: 3005 AN: 41524

American (AMR) AF: 0.00850 AC: 130 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000838 AC: 57 AN: 68032

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.0114 Hom.: 8

Bravo AF: 0.0243

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.55
PhyloP100		-0.088
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs8187674; hg19: chr10-101568013;