rs781908335

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001393392.1(AKR1C2):c.826C>T(p.Arg276Cys) 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000046 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AKR1C2
NM_001393392.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.464

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

46,XY disorder of sex development due to testicular 17,20-desmolase deficiency
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

AKR1C2 links:

ENSG00000224251 (HGNC:):

ENSG00000224251 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01775527).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393392.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AKR1C2	NM_001393392.1	MANE Select	c.826C>T	p.Arg276Cys	missense	Exon 7 of 9	NP_001380321.1	P52895-1
AKR1C2	NM_001354.6		c.826C>T	p.Arg276Cys	missense	Exon 9 of 11	NP_001345.1	P52895-1
AKR1C2	NM_205845.3		c.826C>T	p.Arg276Cys	missense	Exon 8 of 10	NP_995317.1	P52895-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AKR1C2	ENST00000380753.9	TSL:1 MANE Select	c.826C>T	p.Arg276Cys	missense	Exon 7 of 9	ENSP00000370129.4	P52895-1
AKR1C2	ENST00000421196.7	TSL:1	c.748C>T	p.Arg250Cys	missense	Exon 6 of 8	ENSP00000392694.2	B4DK69
AKR1C2	ENST00000867375.1		c.949C>T	p.Arg317Cys	missense	Exon 8 of 10	ENSP00000537434.1

Frequencies

GnomAD3 genomes

AF:

0.0000408

AC:

AN:

147074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00103

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000119

AC:

AN:

75608

AF XY:

0.0000796

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000851

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000696

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000736

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000462

AC:

AN:

1364946

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

669062

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31780

American (AMR)

AF:

0.0000926

AC:

AN:

32384

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22374

East Asian (EAS)

AF:

0.000273

AC:

AN:

36570

South Asian (SAS)

AF:

0.0000824

AC:

AN:

72788

European-Finnish (FIN)

AF:

0.0000203

AC:

AN:

49304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3808

European-Non Finnish (NFE)

AF:

0.0000406

AC:

AN:

1059534

Other (OTH)

AF:

0.00

AC:

AN:

56404

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.323

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000408

AC:

AN:

147074

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71394

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000252

AC:

AN:

39746

American (AMR)

AF:

0.00

AC:

AN:

14554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3400

East Asian (EAS)

AF:

0.00103

AC:

AN:

4836

South Asian (SAS)

AF:

0.00

AC:

AN:

4262

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66886

Other (OTH)

AF:

0.00

AC:

AN:

1970

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000138971), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.383

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000375

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.036

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.0020

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.95

MutationAssessor

Pathogenic

3.7

PhyloP100

-0.46

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-6.8

REVEL

Benign

0.11

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.48

MVP

0.45

MPC

3.8

ClinPred

0.40

GERP RS

-4.7

Varity_R

0.36

gMVP

0.57

Mutation Taster

=66/34

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over