rs781114848

Variant names:

• chr1-26183819-ACC-A
• rs781114848
• NM_006314.3:c.850_851delCC

Your query was ambiguous. Multiple possible variants found:

• chr1-26183819-ACC-A
• chr1-26183819-ACC-AC
• chr1-26183819-ACC-ACCC
• chr1-26183819-ACC-ACCCC

Variant summary

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

The NM_006314.3(CNKSR1):​c.850_851delCC​(p.Pro284ThrfsTer29) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000823 in 1,215,564 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: 28)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: CNKSR1 NM_006314.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• 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.850_851delCC	p.Pro284ThrfsTer29	frameshift	Exon 9 of 21	NP_006305.2	Q53GM7
	CNKSR1	NM_001297647.2		c.871_872delCC	p.Pro291ThrfsTer29	frameshift	Exon 9 of 21	NP_001284576.1	Q969H4-1
	CNKSR1	NM_001297648.2		c.76_77delCC	p.Pro26ThrfsTer29	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.850_851delCC	p.Pro284ThrfsTer29	frameshift	Exon 9 of 21	ENSP00000354609.6	Q969H4-2
	CNKSR1	ENST00000374253.9	TSL:1	c.871_872delCC	p.Pro291ThrfsTer29	frameshift	Exon 9 of 21	ENSP00000363371.5	Q969H4-1
	CNKSR1	ENST00000878394.1		c.871_872delCC	p.Pro291ThrfsTer41	frameshift	Exon 9 of 21	ENSP00000548453.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 8.23e-7 AC: 1 AN: 1215564 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 606714

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26218

American (AMR) AF: 0.00 AC: 0 AN: 38450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18234

East Asian (EAS) AF: 0.00 AC: 0 AN: 20374

South Asian (SAS) AF: 0.00 AC: 0 AN: 82998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4602

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 941454

Other (OTH) AF: 0.00 AC: 0 AN: 45670

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.26

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: rs781114848; hg19: chr1-26510310;