rs200698968

Variant names:

• chr10-4991824-T-A
• rs200698968
• NM_001393392.1:c.929+7A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-4991824-T-A
• chr10-4991824-T-C
• chr10-4991824-T-G

Variant summary

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

The NM_001393392.1(AKR1C2):​c.929+7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 12)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: AKR1C2 NM_001393392.1 splice_region, intron
• Scores: Splicing: ADA: 0.0001058
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 3 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=-0.95).

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.929+7A>T		splice_region intron	N/A	NP_001380321.1	P52895-1
	AKR1C2	NM_001354.6		c.929+7A>T		splice_region intron	N/A	NP_001345.1	P52895-1
	AKR1C2	NM_205845.3		c.929+7A>T		splice_region 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.929+7A>T		splice_region intron	N/A	ENSP00000370129.4	P52895-1
	AKR1C2	ENST00000421196.7	TSL:1	c.851+7A>T		splice_region intron	N/A	ENSP00000392694.2	B4DK69
	AKR1C2	ENST00000867375.1		c.1052+7A>T		splice_region intron	N/A	ENSP00000537434.1

Frequencies

GnomAD3 genomes Cov.: 12

GnomAD4 exome AF: 0.00000272 AC: 1 AN: 367136 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 193740

African (AFR) AF: 0.0000986 AC: 1 AN: 10138

American (AMR) AF: 0.00 AC: 0 AN: 14714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10328

East Asian (EAS) AF: 0.00 AC: 0 AN: 25414

South Asian (SAS) AF: 0.00 AC: 0 AN: 39462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1572

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 217902

Other (OTH) AF: 0.00 AC: 0 AN: 20924

GnomAD4 genome Cov.: 12

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.46
DANN	Benign	0.30
PhyloP100		-1.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.040		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: rs200698968; hg19: chr10-5034016;