rs4460698

Positions:

• chr1-205065360-A-G
• chr1-205065360-A-T

Variant summary

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

The NM_005076.5(CNTN2):​c.1695+98A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,309,428 control chromosomes in the GnomAD database, including 87,595 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 0.30 (8621 hom., cov: 31)
  • Exomes 𝑓: 0.35 (78974 hom.)
• Consequence: CNTN2 NM_005076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

Genes affected

CNTN2 (HGNC:2172): (contactin 2) This gene encodes a member of the contactin family of proteins, part of the immunoglobulin superfamily of cell adhesion molecules. The encoded glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein plays a role in the proliferation, migration, and axon guidance of neurons of the developing cerebellum. A mutation in this gene may be associated with adult myoclonic epilepsy. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN2	NM_005076.5	c.1695+98A>G		intron_variant		ENST00000331830.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN2	ENST00000331830.7	c.1695+98A>G		intron_variant		1	NM_005076.5	P1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45872 AN: 151736 Hom.: 8613 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.322

GnomAD4 exome AF: 0.347 AC: 401726 AN: 1157574 Hom.: 78974 AF XY: 0.353 AC XY: 204893 AN XY: 580906

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.555

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.852

Gnomad4 SAS exome AF: 0.553

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.302 AC: 45887 AN: 151854 Hom.: 8621 Cov.: 31 AF XY: 0.311 AC XY: 23076 AN XY: 74208

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.326

Alfa AF: 0.290 Hom.: 1649

Bravo AF: 0.309

Asia WGS AF: 0.666 AC: 2311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.2
DANN	Benign	0.77

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: rs4460698; hg19: chr1-205034488; COSMIC: COSV59349059; COSMIC: COSV59349059;