rs4950978

Variant names:

• chr1-205055445-C-T
• rs4950978
• NM_005076.5:c.70+2190C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

CNTN2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• epilepsy, familial adult myoclonic, 5

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• benign adult familial myoclonic epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CNTN2	NM_005076.5	c.70+2190C>T		intron_variant	Intron 2 of 22	ENST00000331830.7	NP_005067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN2	ENST00000331830.7	c.70+2190C>T		intron_variant	Intron 2 of 22	1	NM_005076.5	ENSP00000330633.4

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

African (AFR) AF: 0.811 AC: 33621 AN: 41438

American (AMR) AF: 0.364 AC: 5567 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1149 AN: 3472

East Asian (EAS) AF: 0.487 AC: 2515 AN: 5166

South Asian (SAS) AF: 0.443 AC: 2132 AN: 4814

European-Finnish (FIN) AF: 0.270 AC: 2850 AN: 10574

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15199 AN: 67948

Other (OTH) AF: 0.395 AC: 831 AN: 2106

Alfa AF: 0.262 Hom.: 5300

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
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4950978; hg19: chr1-205024573;