Genetic Variant AKR1C2:c.570+1253C>T (chr10-4997372-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001393392.1(AKR1C2):c.570+1253C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,284 control chromosomes in the GnomAD database, including 4,024 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 4018 hom., cov: 32)

Exomes 𝑓: 0.17 ( 6 hom. )

Consequence

AKR1C2
NM_001393392.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0100

Publications

2 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

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	Effect	Exon Rank	Protein
AKR1C2	NM_001393392.1	MANE Select	c.570+1253C>T	intron	N/A	NP_001380321.1
LOC101928051	NR_188167.1		n.333G>A	non_coding_transcript_exon	Exon 3 of 3
AKR1C2	NM_001354.6		c.570+1253C>T	intron	N/A	NP_001345.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AKR1C2	ENST00000380753.9	TSL:1 MANE Select	c.570+1253C>T	intron	N/A	ENSP00000370129.4
AKR1C2	ENST00000421196.7	TSL:1	c.492+1253C>T	intron	N/A	ENSP00000392694.2
ENSG00000224251	ENST00000440414.1	TSL:3	n.294G>A	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31040

AN:

151904

Hom.:

4013

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.261

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.223

GnomAD4 exome

AF:

0.173

AC:

AN:

260

Hom.:

Cov.:

AF XY:

0.158

AC XY:

AN XY:

152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.222

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.131

AC:

AN:

214

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.204

AC:

31063

AN:

152024

Hom.:

4018

Cov.:

AF XY:

0.215

AC XY:

15969

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.111

AC:

4595

AN:

41510

American (AMR)

AF:

0.311

AC:

4753

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

562

AN:

3468

East Asian (EAS)

AF:

0.599

AC:

3085

AN:

5148

South Asian (SAS)

AF:

0.399

AC:

1922

AN:

4814

European-Finnish (FIN)

AF:

0.225

AC:

2372

AN:

10554

Middle Eastern (MID)

AF:

0.269

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.193

AC:

13142

AN:

67948

Other (OTH)

AF:

0.225

AC:

475

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1184

2368

3551

4735

5919

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.197

Hom.:

1296

Bravo

AF:

0.208

Asia WGS

AF:

0.418

AC:

1449

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

(source)

DANN

Benign

0.64

PhyloP100

-0.010

Mutation Taster

=100/0

polymorphism (auto)

(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

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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