chr3-134250569-AGCGGCG-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002958.4. 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
	RYK	NM_002958.4	MANE Select	c.80_85delCGCCGC	p.Pro27_Pro28del	disruptive_inframe_deletion	Exon 1 of 15	NP_002949.2	P34925-1
	RYK	NM_001005861.3		c.80_85delCGCCGC	p.Pro27_Pro28del	disruptive_inframe_deletion	Exon 1 of 15	NP_001005861.1	P34925-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RYK	ENST00000623711.4	TSL:1 MANE Select	c.80_85delCGCCGC	p.Pro27_Pro28del	disruptive_inframe_deletion	Exon 1 of 15	ENSP00000485095.1	P34925-1
	RYK	ENST00000620660.4	TSL:1	c.80_85delCGCCGC	p.Pro27_Pro28del	disruptive_inframe_deletion	Exon 1 of 15	ENSP00000478721.1	P34925-2
	RYK	ENST00000946535.1		c.80_85delCGCCGC	p.Pro27_Pro28del	disruptive_inframe_deletion	Exon 1 of 16	ENSP00000616594.1

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

African (AFR) AF: 0.0000550 AC: 1 AN: 18190

American (AMR) AF: 0.00 AC: 0 AN: 6072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10796

East Asian (EAS) AF: 0.00 AC: 0 AN: 21082

South Asian (SAS) AF: 0.00 AC: 0 AN: 17362

European-Finnish (FIN) AF: 0.0000561 AC: 1 AN: 17810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2414

European-Non Finnish (NFE) AF: 0.00000500 AC: 4 AN: 800514

Other (OTH) AF: 0.00 AC: 0 AN: 35796

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs1284777873; hg19: chr3-133969413;