chr2-18560310-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020905.4(RDH14):​c.263G>C​(p.Arg88Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RDH14
NM_020905.4 missense

Scores

2
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.25
Variant links:
Genes affected
RDH14 (HGNC:19979): (retinol dehydrogenase 14) Enables NADP-retinol dehydrogenase activity. Involved in osteoblast differentiation. Located in cytosol; endoplasmic reticulum; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
NT5C1B-RDH14 (HGNC:38831): (NT5C1B-RDH14 readthrough) This locus represents naturally occurring read-through transcription between the neighboring NT5C1B (5'-nucleotidase, cytosolic IB) and RDH14 (retinol dehydrogenase 14) genes on chromosome 2. Alternative splicing results in multiple transcript variants, one of which encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Nov 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RDH14NM_020905.4 linkc.263G>C p.Arg88Pro missense_variant Exon 1 of 2 ENST00000381249.4 NP_065956.1 Q9HBH5Q53RX3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RDH14ENST00000381249.4 linkc.263G>C p.Arg88Pro missense_variant Exon 1 of 2 1 NM_020905.4 ENSP00000370648.3 Q9HBH5
NT5C1B-RDH14ENST00000532967.5 linkc.1784+3535G>C intron_variant Intron 10 of 10 2 ENSP00000433415.1
NT5C1B-RDH14ENST00000444297.2 linkc.1336-4502G>C intron_variant Intron 8 of 8 2 ENSP00000412639.2 C9J2C7
RDH14ENST00000468071.1 linkn.50+320G>C intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1282264
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
629414
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.263G>C (p.R88P) alteration is located in exon 1 (coding exon 1) of the RDH14 gene. This alteration results from a G to C substitution at nucleotide position 263, causing the arginine (R) at amino acid position 88 to be replaced by a proline (P). 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
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Benign
-0.015
T
BayesDel_noAF
Benign
-0.26
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.57
D
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.70
T
M_CAP
Uncertain
0.27
D
MetaRNN
Pathogenic
0.82
D
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.90
L
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.17
Sift
Benign
0.061
T
Sift4G
Benign
0.092
T
Polyphen
1.0
D
Vest4
0.54
MutPred
0.69
Loss of MoRF binding (P = 0.0045);
MVP
0.53
MPC
0.11
ClinPred
0.96
D
GERP RS
4.3
Varity_R
0.56
gMVP
0.78

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: chr2-18741576; API