14-23990213-C-A

Variant names:

• chr14-23990213-C-A
• NM_198083.4:c.160C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198083.4(DHRS4L2):​c.160C>A​(p.Gln54Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHRS4L2 NM_198083.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45

Genes affected

DHRS4L2 (HGNC:19731): (dehydrogenase/reductase 4 like 2) This gene encodes a member of the short chain dehydrogenase reductase family. The encoded protein may be an NADPH dependent retinol oxidoreductase. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

DHRS4-AS1 (HGNC:23175): (DHRS4 antisense RNA 1)

DHRS4L1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16458938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS4L2	NM_198083.4	c.160C>A	p.Gln54Lys	missense_variant	Exon 2 of 8	ENST00000335125.11	NP_932349.2
DHRS4L2	NM_001193635.1	c.76C>A	p.Gln26Lys	missense_variant	Exon 4 of 9		NP_001180564.1
DHRS4L2	NM_001193636.1	c.-144C>A		5_prime_UTR_variant	Exon 2 of 8		NP_001180565.1
DHRS4L2	NM_001193637.1	c.-144C>A		5_prime_UTR_variant	Exon 2 of 6		NP_001180566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS4L2	ENST00000335125.11	c.160C>A	p.Gln54Lys	missense_variant	Exon 2 of 8	1	NM_198083.4	ENSP00000334801.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.160C>A (p.Q54K) alteration is located in exon 2 (coding exon 2) of the DHRS4L2 gene. This alteration results from a C to A substitution at nucleotide position 160, causing the glutamine (Q) at amino acid position 54 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.77
DEOGEN2	Benign	0.019	T;T;T;.;.;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.92	D;D;D;.;.;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-0.79	T
PROVEAN	Uncertain	-2.4	.;N;N;N;N;N
REVEL	Benign	0.091
Sift	Benign	0.20	.;T;T;T;T;T
Sift4G	Benign	0.36	T;T;T;T;T;T
Polyphen		0.010	.;.;.;.;B;B
Vest4		0.23
MVP		0.83
MPC		0.045
ClinPred		0.11	T
GERP RS		2.4
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-24459422;