Variant 10-4995393-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001393392.1(AKR1C2):c.772C>T(p.Arg258Cys) variant causes a missense 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 Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R258H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0011 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

AKR1C2
NM_001393392.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.60

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010300577).

BP6

Variant 10-4995393-G-A is Benign according to our data. Variant chr10-4995393-G-A is described in ClinVar as [Benign]. Clinvar id is 3042249.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C2	NM_001393392.1 linkuse as main transcript	c.772C>T	p.Arg258Cys	missense_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.772C>T	p.Arg258Cys	missense_variant	7/9	1	NM_001393392.1	P1	P52895-1
AKR1C2	ENST00000421196.7 linkuse as main transcript	c.694C>T	p.Arg232Cys	missense_variant	6/8	1
AKR1C2	ENST00000460124.5 linkuse as main transcript	n.2232C>T		non_coding_transcript_exon_variant	6/8	5

Frequencies

GnomAD3 genomes

AF:

0.000148

AC:

AN:

148276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000494

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000633

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00146

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000194

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000497

GnomAD3 exomes

AF:

0.00636

AC:

832

AN:

130808

Hom.:

AF XY:

0.00529

AC XY:

364

AN XY:

68776

show subpopulations

Gnomad AFR exome

AF:

0.000307

Gnomad AMR exome

AF:

0.0313

Gnomad ASJ exome

AF:

0.00217

Gnomad EAS exome

AF:

0.0176

Gnomad SAS exome

AF:

0.000986

Gnomad FIN exome

AF:

0.00373

Gnomad NFE exome

AF:

0.000370

Gnomad OTH exome

AF:

0.00287

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00113

AC:

1636

AN:

1441716

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

717

AN XY:

716028

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0305

Gnomad4 ASJ exome

AF:

0.000896

Gnomad4 EAS exome

AF:

0.00609

Gnomad4 SAS exome

AF:

0.000235

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.0000580

Gnomad4 OTH exome

AF:

0.000556

GnomAD4 genome

AF:

0.000148

AC:

AN:

148392

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

AN XY:

72094

show subpopulations

Gnomad4 AFR

AF:

0.0000493

Gnomad4 AMR

AF:

0.000632

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00147

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000194

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.000492

Alfa

AF:

0.00130

Hom.:

ExAC

AF:

0.00844

AC:

933

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AKR1C2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as 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

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

0.052

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Pathogenic

3.9

H;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-7.2

D;D

REVEL

Uncertain

0.30

Sift

Benign

0.033

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.99

D;D

Vest4

0.51

MVP

0.44

MPC

3.0

ClinPred

0.095

GERP RS

-0.078

Varity_R

0.79

gMVP

0.67

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