Variant 10-4995382-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_001393392.1(AKR1C2):c.783G>A(p.Leu261=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0015 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

AKR1C2
NM_001393392.1 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.14

Variant links:

Genes affected

AKR1C2 (HGNC:385): (aldo-keto reductase family 1 member C2) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols using NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme binds bile acid with high affinity, and shows minimal 3-alpha-hydroxysteroid dehydrogenase activity. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

AKR1C2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-4995382-C-T is Benign according to our data. Variant chr10-4995382-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3056884.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-4995382-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-3.14 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C2	NM_001393392.1 linkuse as main transcript	c.783G>A	p.Leu261=	synonymous_variant	7/9	ENST00000380753.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C2	ENST00000380753.9 linkuse as main transcript	c.783G>A	p.Leu261=	synonymous_variant	7/9	1	NM_001393392.1	P1	P52895-1
AKR1C2	ENST00000421196.7 linkuse as main transcript	c.705G>A	p.Leu235=	synonymous_variant	6/8	1
AKR1C2	ENST00000460124.5 linkuse as main transcript	n.2243G>A		non_coding_transcript_exon_variant	6/8	5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

383

AN:

143512

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.0103

Gnomad EAS

AF:

0.000202

Gnomad SAS

AF:

0.00370

Gnomad FIN

AF:

0.00107

Gnomad MID

AF:

0.00329

Gnomad NFE

AF:

0.00322

Gnomad OTH

AF:

0.00365

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00148

AC:

2056

AN:

1391382

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

1294

AN XY:

689558

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.00599

Gnomad4 EAS exome

AF:

0.000485

Gnomad4 SAS exome

AF:

0.00359

Gnomad4 FIN exome

AF:

0.000948

Gnomad4 NFE exome

AF:

0.00123

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00267

AC:

383

AN:

143618

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

177

AN XY:

69986

show subpopulations

Gnomad4 AFR

AF:

0.00179

Gnomad4 AMR

AF:

0.00267

Gnomad4 ASJ

AF:

0.0103

Gnomad4 EAS

AF:

0.000202

Gnomad4 SAS

AF:

0.00370

Gnomad4 FIN

AF:

0.00107

Gnomad4 NFE

AF:

0.00322

Gnomad4 OTH

AF:

0.00362

Alfa

AF:

0.00664

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AKR1C2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 03, 2019

This 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.7

DANN

Benign

0.92

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