3-134250593-AG-AGG

Variant names:

• chr3-134250593-A-AG
• rs587770426
• NM_002958.4:c.61dupC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002958.4(RYK):​c.61dupC​(p.Leu21ProfsTer60) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RYK NM_002958.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656

Genes affected

RYK (HGNC:10481): (receptor like tyrosine kinase) The protein encoded by this gene is an atypical member of the family of growth factor receptor protein tyrosine kinases, differing from other members at a number of conserved residues in the activation and nucleotide binding domains. This gene product belongs to a subfamily whose members do not appear to be regulated by phosphorylation in the activation segment. It has been suggested that mediation of biological activity by recruitment of a signaling-competent auxiliary protein may occur through an as yet uncharacterized mechanism. The encoded protein has a leucine-rich extracellular domain with a WIF-type Wnt binding region, a single transmembrane domain, and an intracellular tyrosine kinase domain. This protein is involved in stimulating Wnt signaling pathways such as the regulation of axon pathfinding. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
RYK	NM_002958.4	c.61dupC	p.Leu21ProfsTer60	frameshift_variant	Exon 1 of 15	ENST00000623711.4	NP_002949.2
RYK	NM_001005861.3	c.61dupC	p.Leu21ProfsTer60	frameshift_variant	Exon 1 of 15		NP_001005861.1
RYK	XR_007095716.1	n.266dupC		non_coding_transcript_exon_variant	Exon 1 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYK	ENST00000623711.4	c.61dupC	p.Leu21ProfsTer60	frameshift_variant	Exon 1 of 15	1	NM_002958.4	ENSP00000485095.1
RYK	ENST00000620660.4	c.61dupC	p.Leu21ProfsTer60	frameshift_variant	Exon 1 of 15	1		ENSP00000478721.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 1.00 AC: 4 AN: 4 Hom.: 2 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad NFE exome AF: 1.00

GnomAD4 exome Cov.: 16

GnomAD4 genome Cov.: 31

Alfa AF: 1.00 Hom.: 2231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs587770426; hg19: chr3-133969437;