rs8668

chr20-62389008-A-G

Variant summary

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

The NM_031215.3(CABLES2):c.*1963T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 157,602 control chromosomes in the GnomAD database, including 9,139 homozygotes. 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 0.33 (8887 hom., cov: 35)
  • Exomes 𝑓: 0.30 (252 hom.)
• Consequence: CABLES2 NM_031215.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750

Genes affected

CABLES2 (HGNC:16143): (Cdk5 and Abl enzyme substrate 2) Predicted to be involved in cell division and regulation of cell cycle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CABLES2	NM_031215.3	c.*1963T>C		3_prime_UTR_variant	10/10	ENST00000279101.10
CABLES2	XM_047440530.1	c.*1963T>C		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CABLES2	ENST00000279101.10	c.*1963T>C		3_prime_UTR_variant	10/10	5	NM_031215.3	P1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49975 AN: 152124 Hom.: 8876 Cov.: 35

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.322

GnomAD4 exome AF: 0.296 AC: 1589 AN: 5360 Hom.: 252 Cov.: 0 AF XY: 0.288 AC XY: 823 AN XY: 2856

Gnomad4 AFR exome AF: 0.367

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.298

GnomAD4 genome AF: 0.329 AC: 50026 AN: 152242 Hom.: 8887 Cov.: 35 AF XY: 0.324 AC XY: 24084 AN XY: 74430

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.318

Alfa AF: 0.306 Hom.: 9257

Bravo AF: 0.341

Asia WGS AF: 0.207 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.6
Dann	Benign	0.40

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: rs8668; hg19: chr20-60964064; COSMIC: COSV54158245; COSMIC: COSV54158245;