1-205065360-A-T

Variant names:

• chr1-205065360-A-T
• rs4460698
• NM_005076.5:c.1695+98A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005076.5(CNTN2):​c.1695+98A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNTN2 NM_005076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN2	NM_005076.5	c.1695+98A>T		intron_variant	Intron 13 of 22	ENST00000331830.7	NP_005067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN2	ENST00000331830.7	c.1695+98A>T		intron_variant	Intron 13 of 22	1	NM_005076.5	ENSP00000330633.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1159562 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 581880

African (AFR) AF: 0.00 AC: 0 AN: 26158

American (AMR) AF: 0.00 AC: 0 AN: 33130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19906

East Asian (EAS) AF: 0.00 AC: 0 AN: 38144

South Asian (SAS) AF: 0.00 AC: 0 AN: 69620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4942

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 873072

Other (OTH) AF: 0.00 AC: 0 AN: 49792

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.79
PhyloP100		-0.20
PromoterAI		-0.0028	Neutral

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: rs4460698; hg19: chr1-205034488;