rs4950978

chr1-205055445-C-T

Variant summary

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

The NM_005076.5(CNTN2):c.70+2190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,998 control chromosomes in the GnomAD database, including 18,379 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 0.42 (18379 hom., cov: 32)
• Consequence: CNTN2 NM_005076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN2	NM_005076.5	c.70+2190C>T		intron_variant		ENST00000331830.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN2	ENST00000331830.7	c.70+2190C>T		intron_variant		1	NM_005076.5	P1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64161 AN: 151880 Hom.: 18326 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.423 AC: 64270 AN: 151998 Hom.: 18379 Cov.: 32 AF XY: 0.425 AC XY: 31597 AN XY: 74310

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.395

Alfa AF: 0.272 Hom.: 4074

Bravo AF: 0.447

Asia WGS AF: 0.487 AC: 1690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.079
Dann	Benign	0.56

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: rs4950978; hg19: chr1-205024573;