16-22166169-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001394319.2(SDR42E2):c.56-81A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00671 in 431,390 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (12 hom.)
• Consequence: SDR42E2 NM_001394319.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.169

Genes affected

SDR42E2 (HGNC:35414): (short chain dehydrogenase/reductase family 42E, member 2) Predicted to enable oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. Predicted to be involved in steroid biosynthetic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-22166169-A-T is Benign according to our data. Variant chr16-22166169-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2646310.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDR42E2	NM_001394319.2	c.56-81A>T		intron_variant		ENST00000602312.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDR42E2	ENST00000602312.3	c.56-81A>T		intron_variant		5	NM_001394319.2	P1
SDR42E2	ENST00000686682.1	c.587A>T	p.Glu196Val	missense_variant	2/9
SDR42E2	ENST00000684942.1	c.587A>T	p.Glu196Val	missense_variant, NMD_transcript_variant	2/11
SDR42E2	ENST00000687571.1	c.587A>T	p.Glu196Val	missense_variant, NMD_transcript_variant	2/10

Frequencies

GnomAD3 genomes AF: 0.00599 AC: 905 AN: 151186 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00201

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.00428

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00804

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00952

Gnomad OTH AF: 0.00289

GnomAD4 exome AF: 0.00710 AC: 1989 AN: 280082 Hom.: 12 AF XY: 0.00720 AC XY: 1046 AN XY: 145348

Gnomad4 AFR exome AF: 0.00191

Gnomad4 AMR exome AF: 0.00460

Gnomad4 ASJ exome AF: 0.00429

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00110

Gnomad4 FIN exome AF: 0.00732

Gnomad4 NFE exome AF: 0.00895

Gnomad4 OTH exome AF: 0.00644

GnomAD4 genome AF: 0.00598 AC: 905 AN: 151308 Hom.: 7 Cov.: 32 AF XY: 0.00558 AC XY: 413 AN XY: 73970

Gnomad4 AFR AF: 0.00200

Gnomad4 AMR AF: 0.00428

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00804

Gnomad4 NFE AF: 0.00952

Gnomad4 OTH AF: 0.00286

Alfa AF: 0.00709 Hom.: 1

Bravo AF: 0.00564

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

SDR42E2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.5
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs79651149; hg19: chr16-22177490;