2-18560274-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_020905.4(RDH14):c.299A>G(p.Glu100Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,355,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

RDH14
NM_020905.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.192

Publications

0 publications found

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]

RDH14 links:

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]

NT5C1B-RDH14 links:

LOC105373456 (HGNC:):

LOC105373456 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13202664).

BP6

Variant 2-18560274-T-C is Benign according to our data. Variant chr2-18560274-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2493551.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020905.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RDH14	NM_020905.4	MANE Select	c.299A>G	p.Glu100Gly	missense	Exon 1 of 2	NP_065956.1	Q53RX3
NT5C1B-RDH14	NM_001199103.2		c.1336-4466A>G		intron	N/A	NP_001186032.1
NT5C1B-RDH14	NM_001199104.2		c.1784+3571A>G		intron	N/A	NP_001186033.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RDH14	ENST00000381249.4	TSL:1 MANE Select	c.299A>G	p.Glu100Gly	missense	Exon 1 of 2	ENSP00000370648.3	Q9HBH5
NT5C1B-RDH14	ENST00000532967.5	TSL:2	c.1784+3571A>G		intron	N/A	ENSP00000433415.1
RDH14	ENST00000870568.1		c.299A>G	p.Glu100Gly	missense	Exon 1 of 2	ENSP00000540627.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000989

AC:

AN:

101086

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000279

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.38e-7

AC:

AN:

1355558

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

668550

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27892

American (AMR)

AF:

0.00

AC:

AN:

32950

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24122

East Asian (EAS)

AF:

0.00

AC:

AN:

31720

South Asian (SAS)

AF:

0.00

AC:

AN:

77548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4070

European-Non Finnish (NFE)

AF:

9.37e-7

AC:

AN:

1067460

Other (OTH)

AF:

0.00

AC:

AN:

56562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.16

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.27

M_CAP

Pathogenic

0.61

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.39

PhyloP100

-0.19

PROVEAN

Benign

-0.030

REVEL

Benign

0.12

Sift

Benign

0.10

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.075

MutPred

0.35

Gain of catalytic residue at E100 (P = 0.1135)

MVP

0.40

MPC

0.045

ClinPred

0.035

GERP RS

-4.2

PromoterAI

0.23

Neutral

(source)

Varity_R

0.038

gMVP

0.39

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over