X-21521798-C-T

Position:

• chrX-21521798-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014927.5(CNKSR2):​c.958-5069C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00671 in 110,605 control chromosomes in the GnomAD database, including 4 homozygotes. There are 209 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0067 (4 hom., 209 hem., cov: 22)
• Consequence: CNKSR2 NM_014927.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285

Genes affected

CNKSR2 (HGNC:19701): (connector enhancer of kinase suppressor of Ras 2) This gene encodes a multidomain protein that functions as a scaffold protein to mediate the mitogen-activated protein kinase pathways downstream from Ras. This gene product is induced by vitamin D and inhibits apoptosis in certain cancer cells. It may also play a role in ternary complex assembly of synaptic proteins at the postsynaptic membrane and coupling of signal transduction to membrane/cytoskeletal remodeling. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00671 (742/110605) while in subpopulation AFR AF= 0.0227 (698/30707). AF 95% confidence interval is 0.0213. There are 4 homozygotes in gnomad4. There are 209 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNKSR2	NM_014927.5	c.958-5069C>T		intron_variant		ENST00000379510.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNKSR2	ENST00000379510.5	c.958-5069C>T		intron_variant		1	NM_014927.5	P1

Frequencies

GnomAD3 genomes AF: 0.00668 AC: 738 AN: 110555 Hom.: 3 Cov.: 22 AF XY: 0.00626 AC XY: 208 AN XY: 33225

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000382

Gnomad OTH AF: 0.00401

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00671 AC: 742 AN: 110605 Hom.: 4 Cov.: 22 AF XY: 0.00628 AC XY: 209 AN XY: 33285

Gnomad4 AFR AF: 0.0227

Gnomad4 AMR AF: 0.00328

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000745

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000382

Gnomad4 OTH AF: 0.00396

Alfa AF: 0.00279 Hom.: 11

Bravo AF: 0.00801

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.0
DANN	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs16981582; hg19: chrX-21539916;