10-99798989-G-T

Position:

• chr10-99798989-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000392.5(ABCC2):​c.868-218G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,924 control chromosomes in the GnomAD database, including 21,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.53 (21326 hom., cov: 31)
• Consequence: ABCC2 NM_000392.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.604

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 10-99798989-G-T is Benign according to our data. Variant chr10-99798989-G-T is described in ClinVar as [Benign]. Clinvar id is 1233362.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC2	NM_000392.5	c.868-218G>T		intron_variant		ENST00000647814.1	NP_000383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC2	ENST00000647814.1	c.868-218G>T		intron_variant			NM_000392.5	ENSP00000497274	P1
ABCC2	ENST00000648324.1	c.*705-222G>T		intron_variant, NMD_transcript_variant				ENSP00000497248
ABCC2	ENST00000649493.1	c.*683-218G>T		intron_variant, NMD_transcript_variant				ENSP00000496847
ABCC2	ENST00000649932.1	c.*390-218G>T		intron_variant, NMD_transcript_variant				ENSP00000498120

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79880 AN: 151806 Hom.: 21319 Cov.: 31

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.545

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.526 AC: 79915 AN: 151924 Hom.: 21326 Cov.: 31 AF XY: 0.523 AC XY: 38791 AN XY: 74232

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.547

Alfa AF: 0.563 Hom.: 13615

Bravo AF: 0.522

Asia WGS AF: 0.481 AC: 1674 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.9
DANN	Benign	0.83

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

Other links and lift over

dbSNP: rs2756109; hg19: chr10-101558746;