3-134250569-AGCGGCGGCG-AGCG

Variant names:

• chr3-134250569-AGCGGCG-A
• rs1284777873
• NM_002958.4:c.80_85delCGCCGC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3 BS2

The NM_002958.4(RYK):​c.80_85delCGCCGC​(p.Pro27_Pro28del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000645 in 930,036 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: RYK NM_002958.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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 Likely_benign. Variant got -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_002958.4
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYK	NM_002958.4	c.80_85delCGCCGC	p.Pro27_Pro28del	disruptive_inframe_deletion	Exon 1 of 15	ENST00000623711.4	NP_002949.2
RYK	NM_001005861.3	c.80_85delCGCCGC	p.Pro27_Pro28del	disruptive_inframe_deletion	Exon 1 of 15		NP_001005861.1
RYK	XR_007095716.1	n.285_290delCGCCGC		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.80_85delCGCCGC	p.Pro27_Pro28del	disruptive_inframe_deletion	Exon 1 of 15	1	NM_002958.4	ENSP00000485095.1
RYK	ENST00000620660.4	c.80_85delCGCCGC	p.Pro27_Pro28del	disruptive_inframe_deletion	Exon 1 of 15	1		ENSP00000478721.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000645 AC: 6 AN: 930036 Hom.: 0 AF XY: 0.00000681 AC XY: 3 AN XY: 440560

Gnomad4 AFR exome AF: 0.0000550

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000561

Gnomad4 NFE exome AF: 0.00000500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

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: rs1284777873; hg19: chr3-133969413;