2-18555567-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020905.4(RDH14):​c.635A>G​(p.Asn212Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N212I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RDH14
NM_020905.4 missense

Scores

4
14

Clinical Significance

Not reported in ClinVar

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]

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ACMG classification

Classification made for transcript

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=0.2341854).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RDH14NM_020905.4 linkc.635A>G p.Asn212Ser missense_variant Exon 2 of 2 ENST00000381249.4 NP_065956.1 Q9HBH5Q53RX3
NT5C1B-RDH14NM_001199103.2 linkc.1577A>G p.Asn526Ser missense_variant Exon 9 of 9 NP_001186032.1
NT5C1B-RDH14NM_001199104.2 linkc.*217A>G 3_prime_UTR_variant Exon 11 of 11 NP_001186033.1 Q96P26-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RDH14ENST00000381249.4 linkc.635A>G p.Asn212Ser missense_variant Exon 2 of 2 1 NM_020905.4 ENSP00000370648.3 Q9HBH5
NT5C1B-RDH14ENST00000532967 linkc.*217A>G 3_prime_UTR_variant Exon 11 of 11 2 ENSP00000433415.1
NT5C1B-RDH14ENST00000444297.2 linkc.1577A>G p.Asn526Ser missense_variant Exon 9 of 9 2 ENSP00000412639.2 C9J2C7
RDH14ENST00000468071.1 linkn.292A>G non_coding_transcript_exon_variant Exon 2 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;.
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.14
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.81
T;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.23
T;T
MetaSVM
Uncertain
-0.19
T
MutationAssessor
Benign
0.030
N;.
PROVEAN
Uncertain
-2.5
N;N
REVEL
Benign
0.17
Sift
Benign
0.56
T;T
Sift4G
Benign
0.48
T;T
Polyphen
0.013
B;B
Vest4
0.16
MutPred
0.69
.;Gain of glycosylation at N526 (P = 0.0364);
MVP
0.92
MPC
0.036
ClinPred
0.23
T
GERP RS
3.3
Varity_R
0.051
gMVP
0.74

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: chr2-18736833; API