Genetic Variant AKR1C2:c.*297C>T (chr10-4989699-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_001393392.1(AKR1C2):c.*297C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 460,078 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000039 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

AKR1C2
NM_001393392.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.07

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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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	UniProt
AKR1C2	NM_001393392.1	MANE Select	c.*297C>T	3_prime_UTR	Exon 9 of 9	NP_001380321.1	P52895-1
AKR1C2	NM_001354.6		c.*297C>T	3_prime_UTR	Exon 11 of 11	NP_001345.1	P52895-1
AKR1C2	NM_205845.3		c.*297C>T	3_prime_UTR	Exon 10 of 10	NP_995317.1	P52895-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AKR1C2	ENST00000380753.9	TSL:1 MANE Select	c.*297C>T	3_prime_UTR	Exon 9 of 9	ENSP00000370129.4	P52895-1
AKR1C2	ENST00000421196.7	TSL:1	c.*297C>T	3_prime_UTR	Exon 8 of 8	ENSP00000392694.2	B4DK69
AKR1C2	ENST00000867375.1		c.*297C>T	downstream_gene	N/A	ENSP00000537434.1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

308018

Hom.:

Cov.:

AF XY:

0.0000247

AC XY:

AN XY:

161630

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6932

American (AMR)

AF:

0.00

AC:

AN:

7496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9762

East Asian (EAS)

AF:

0.000300

AC:

AN:

16676

South Asian (SAS)

AF:

0.0000683

AC:

AN:

29288

European-Finnish (FIN)

AF:

0.0000349

AC:

AN:

28672

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1400

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

189688

Other (OTH)

AF:

0.00

AC:

AN:

18104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

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

AF:

0.0000395

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41360

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000769

AC:

AN:

5202

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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.:

Bravo

AF:

0.0000642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.10

(source)

DANN

Benign

0.64

PhyloP100

-2.1

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