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rs717620

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000392.5(ABCC2):c.-24C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,610,598 control chromosomes in the GnomAD database, including 29,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2125 hom., cov: 33)
Exomes 𝑓: 0.19 ( 27698 hom. )

Consequence

ABCC2
NM_000392.5 5_prime_UTR

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.07
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 10-99782821-C-T is Benign according to our data. Variant chr10-99782821-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 298437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCC2NM_000392.5 linkuse as main transcriptc.-24C>T 5_prime_UTR_variant 1/32 ENST00000647814.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCC2ENST00000647814.1 linkuse as main transcriptc.-24C>T 5_prime_UTR_variant 1/32 NM_000392.5 P1

Frequencies

GnomAD3 genomes
AF:
0.155
AC:
23555
AN:
152080
Hom.:
2127
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0618
Gnomad AMI
AF:
0.227
Gnomad AMR
AF:
0.163
Gnomad ASJ
AF:
0.211
Gnomad EAS
AF:
0.207
Gnomad SAS
AF:
0.117
Gnomad FIN
AF:
0.190
Gnomad MID
AF:
0.148
Gnomad NFE
AF:
0.198
Gnomad OTH
AF:
0.178
GnomAD3 exomes
AF:
0.171
AC:
42814
AN:
251040
Hom.:
3942
AF XY:
0.171
AC XY:
23245
AN XY:
135676
show subpopulations
Gnomad AFR exome
AF:
0.0565
Gnomad AMR exome
AF:
0.130
Gnomad ASJ exome
AF:
0.199
Gnomad EAS exome
AF:
0.213
Gnomad SAS exome
AF:
0.113
Gnomad FIN exome
AF:
0.195
Gnomad NFE exome
AF:
0.200
Gnomad OTH exome
AF:
0.183
GnomAD4 exome
AF:
0.190
AC:
276603
AN:
1458400
Hom.:
27698
Cov.:
31
AF XY:
0.188
AC XY:
136569
AN XY:
725676
show subpopulations
Gnomad4 AFR exome
AF:
0.0536
Gnomad4 AMR exome
AF:
0.132
Gnomad4 ASJ exome
AF:
0.201
Gnomad4 EAS exome
AF:
0.205
Gnomad4 SAS exome
AF:
0.112
Gnomad4 FIN exome
AF:
0.194
Gnomad4 NFE exome
AF:
0.202
Gnomad4 OTH exome
AF:
0.183
GnomAD4 genome
AF:
0.155
AC:
23547
AN:
152198
Hom.:
2125
Cov.:
33
AF XY:
0.156
AC XY:
11601
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.0617
Gnomad4 AMR
AF:
0.163
Gnomad4 ASJ
AF:
0.211
Gnomad4 EAS
AF:
0.206
Gnomad4 SAS
AF:
0.117
Gnomad4 FIN
AF:
0.190
Gnomad4 NFE
AF:
0.199
Gnomad4 OTH
AF:
0.179
Alfa
AF:
0.191
Hom.:
6167
Bravo
AF:
0.147
Asia WGS
AF:
0.154
AC:
533
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jul 18, 2017- -
ABCC2-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 11, 2023This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 18, 2021This variant is associated with the following publications: (PMID: 19415824, 22664480, 16788565, 24743544, 19890061, 21451505) -
Dubin-Johnson syndrome Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaMar 06, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
14
Dann
Benign
0.49

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.

Other links and lift over

dbSNP: rs717620; hg19: chr10-101542578; COSMIC: COSV64970575; API