10-4995068-T-A

Variant names:

• chr10-4995068-T-A
• rs2801887
• NM_001393392.1:c.846+251A>T

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112
• Publications: 0 publications found

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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: 0 AN: 54796 Hom.: 0 Cov.: 7

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: 0 AN: 54796 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 24820

African (AFR) AF: 0.00 AC: 0 AN: 12154

American (AMR) AF: 0.00 AC: 0 AN: 5006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1118

East Asian (EAS) AF: 0.00 AC: 0 AN: 1398

South Asian (SAS) AF: 0.00 AC: 0 AN: 1166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 120

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 29010

Other (OTH) AF: 0.00 AC: 0 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
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

Other links and lift over

dbSNP: rs2801887; hg19: chr10-5037260;