rs779464218

Variant names:

• chr2-18560458-CG-C
• rs779464218
• NM_020905.4:c.114delC

Your query was ambiguous. Multiple possible variants found:

• chr2-18560458-CG-C
• chr2-18560458-CG-CGG

Variant summary

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

The NM_020905.4(RDH14):​c.114delC​(p.Gly39AlafsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,361,022 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: RDH14 NM_020905.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 1 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]

LOC105373456 (HGNC:):

ACMG classification

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RDH14	NM_020905.4	c.114delC	p.Gly39AlafsTer9	frameshift_variant	Exon 1 of 2	ENST00000381249.4	NP_065956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RDH14	ENST00000381249.4	c.114delC	p.Gly39AlafsTer9	frameshift_variant	Exon 1 of 2	1	NM_020905.4	ENSP00000370648.3
NT5C1B-RDH14	ENST00000532967.5	c.1784+3386delC		intron_variant	Intron 10 of 10	2		ENSP00000433415.1
NT5C1B-RDH14	ENST00000444297.2	c.1336-4651delC		intron_variant	Intron 8 of 8	2		ENSP00000412639.2
RDH14	ENST00000468071.1	n.50+171delC		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.35e-7 AC: 1 AN: 1361022 Hom.: 0 Cov.: 31 AF XY: 0.00000149 AC XY: 1 AN XY: 671578

African (AFR) AF: 0.00 AC: 0 AN: 28116

American (AMR) AF: 0.00 AC: 0 AN: 33504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24230

East Asian (EAS) AF: 0.00 AC: 0 AN: 32666

South Asian (SAS) AF: 0.00 AC: 0 AN: 77246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4170

European-Non Finnish (NFE) AF: 9.34e-7 AC: 1 AN: 1070946

Other (OTH) AF: 0.00 AC: 0 AN: 56814

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.085
Mutation Taster		=55/145	disease causing (fs/PTC)

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: rs779464218; hg19: chr2-18741724;