dbSNP rs2801887: AKR1C2:c.846+251A>T (chr10-4995068-T-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.846+251A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 7)

Failed GnomAD Quality Control

Consequence

AKR1C2
NM_001393392.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.112

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:

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 (BayesDel_noAF=-0.97).

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.846+251A>T	intron	N/A	NP_001380321.1	P52895-1
AKR1C2	NM_001354.6		c.846+251A>T	intron	N/A	NP_001345.1	P52895-1
AKR1C2	NM_205845.3		c.846+251A>T	intron	N/A	NP_995317.1	P52895-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AKR1C2	ENST00000380753.9	TSL:1 MANE Select	c.846+251A>T	intron	N/A	ENSP00000370129.4	P52895-1
AKR1C2	ENST00000421196.7	TSL:1	c.768+251A>T	intron	N/A	ENSP00000392694.2	B4DK69
AKR1C2	ENST00000867375.1		c.969+251A>T	intron	N/A	ENSP00000537434.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

54796

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

54796

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

24820

African (AFR)

AF:

0.00

AC:

AN:

12154

American (AMR)

AF:

0.00

AC:

AN:

5006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1118

East Asian (EAS)

AF:

0.00

AC:

AN:

1398

South Asian (SAS)

AF:

0.00

AC:

AN:

1166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3762

Middle Eastern (MID)

AF:

0.00

AC:

AN:

120

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

29010

Other (OTH)

AF:

0.00

AC:

AN:

652

Alfa

AF:

0.00

Hom.:

886

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.5

(source)

DANN

Benign

0.45

PhyloP100

-0.11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over