1-26183819-ACC-ACCC

Variant names:

• chr1-26183820-C-CC
• NM_006314.3:c.851dupC

Variant summary

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

The NM_006314.3(CNKSR1):​c.851dupC​(p.Gln285ThrfsTer29) 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. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 28)
• Consequence: CNKSR1 NM_006314.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 0 publications found

Genes affected

CNKSR1 (HGNC:19700): (connector enhancer of kinase suppressor of Ras 1) This gene encodes a protein containing several motifs involved in protein-protein interaction, including PDZ, PH (Pleckstrin homology), and SAM (sterile alpha motif) domains. The encoded protein acts as a scaffold component for receptor tyrosine kinase signaling and may mediate crosstalk between different signaling pathways. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

CNKSR1 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

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_006314.3. 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
	CNKSR1	NM_006314.3	MANE Select	c.851dupC	p.Gln285ThrfsTer29	frameshift	Exon 9 of 21	NP_006305.2	Q53GM7
	CNKSR1	NM_001297647.2		c.872dupC	p.Gln292ThrfsTer29	frameshift	Exon 9 of 21	NP_001284576.1	Q969H4-1
	CNKSR1	NM_001297648.2		c.77dupC	p.Gln27ThrfsTer29	frameshift	Exon 9 of 21	NP_001284577.1	G3V160

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNKSR1	ENST00000361530.11	TSL:1 MANE Select	c.851dupC	p.Gln285ThrfsTer29	frameshift	Exon 9 of 21	ENSP00000354609.6	Q969H4-2
	CNKSR1	ENST00000374253.9	TSL:1	c.872dupC	p.Gln292ThrfsTer29	frameshift	Exon 9 of 21	ENSP00000363371.5	Q969H4-1
	CNKSR1	ENST00000878394.1		c.872dupC	p.Gln292ThrfsTer41	frameshift	Exon 9 of 21	ENSP00000548453.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-26510311;