2-18555567-T-A

Variant names:

• chr2-18555567-T-A
• rs138843648
• NM_020905.4:c.635A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020905.4(RDH14):​c.635A>T​(p.Asn212Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RDH14 NM_020905.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.25
• Publications: 0 publications found

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]

ENSG00000304724 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH14	NM_020905.4	MANE Select	c.635A>T	p.Asn212Ile	missense	Exon 2 of 2	NP_065956.1	Q53RX3
	NT5C1B-RDH14	NM_001199103.2		c.1577A>T	p.Asn526Ile	missense	Exon 9 of 9	NP_001186032.1
	NT5C1B-RDH14	NM_001199104.2		c.*217A>T		3_prime_UTR	Exon 11 of 11	NP_001186033.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH14	ENST00000381249.4	TSL:1 MANE Select	c.635A>T	p.Asn212Ile	missense	Exon 2 of 2	ENSP00000370648.3	Q9HBH5
	NT5C1B-RDH14	ENST00000532967.5	TSL:2	c.*217A>T		3_prime_UTR	Exon 11 of 11	ENSP00000433415.1
	NT5C1B-RDH14	ENST00000444297.2	TSL:2	c.1577A>T	p.Asn526Ile	missense	Exon 9 of 9	ENSP00000412639.2	C9J2C7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	0.60	D
MutationAssessor	Benign	2.0	M
PhyloP100		4.3
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.54	P
Vest4		0.61
MVP		0.99
MPC		0.16
ClinPred		0.96	D
GERP RS		3.3
Varity_R		0.41
gMVP		0.89
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs138843648; hg19: chr2-18736833;