rs6528025

Positions:

• chrX-21598242-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014927.5(CNKSR2):​c.1976+2847G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 110,590 control chromosomes in the GnomAD database, including 2,834 homozygotes. There are 4,289 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 0.15 (2834 hom., 4289 hem., cov: 22)
• Consequence: CNKSR2 NM_014927.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNKSR2	NM_014927.5	c.1976+2847G>C		intron_variant		ENST00000379510.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNKSR2	ENST00000379510.5	c.1976+2847G>C		intron_variant		1	NM_014927.5	P1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 16192 AN: 110545 Hom.: 2831 Cov.: 22 AF XY: 0.130 AC XY: 4272 AN XY: 32867

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0608

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.00646

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.00664

Gnomad MID AF: 0.0468

Gnomad NFE AF: 0.00287

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.147 AC: 16223 AN: 110590 Hom.: 2834 Cov.: 22 AF XY: 0.130 AC XY: 4289 AN XY: 32922

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.0606

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.00648

Gnomad4 SAS AF: 0.0163

Gnomad4 FIN AF: 0.00664

Gnomad4 NFE AF: 0.00287

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0888 Hom.: 563

Bravo AF: 0.168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.69

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: rs6528025; hg19: chrX-21616360;