rs2854466

Variant names:

• chr10-4997372-G-A
• rs2854466
• NM_001393392.1:c.570+1253C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-4997372-G-A
• chr10-4997372-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 2 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

ENSG00000224251 (HGNC:):

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C2	NM_001393392.1	MANE Select	c.570+1253C>T		intron	N/A	NP_001380321.1	P52895-1
	AKR1C2	NM_001354.6		c.570+1253C>T		intron	N/A	NP_001345.1	P52895-1
	AKR1C2	NM_205845.3		c.570+1253C>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.570+1253C>T		intron	N/A	ENSP00000370129.4	P52895-1
	AKR1C2	ENST00000421196.7	TSL:1	c.492+1253C>T		intron	N/A	ENSP00000392694.2	B4DK69
	AKR1C2	ENST00000867375.1		c.693+1253C>T		intron	N/A	ENSP00000537434.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31040 AN: 151904 Hom.: 4013 Cov.: 32

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: 45 AN: 260 Hom.: 6 Cov.: 0 AF XY: 0.158 AC XY: 24 AN XY: 152

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.222 AC: 4 AN: 18

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.500 AC: 4 AN: 8

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.131 AC: 28 AN: 214

Other (OTH) AF: 0.250 AC: 2 AN: 8

GnomAD4 genome AF: 0.204 AC: 31063 AN: 152024 Hom.: 4018 Cov.: 32 AF XY: 0.215 AC XY: 15969 AN XY: 74288

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: 78 AN: 290

European-Non Finnish (NFE) AF: 0.193 AC: 13142 AN: 67948

Other (OTH) AF: 0.225 AC: 475 AN: 2108

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
DANN	Benign	0.64
PhyloP100		-0.010
Mutation Taster		=100/0	polymorphism (auto)

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: rs2854466; hg19: chr10-5039564;