rs1470637

Variant names:

• chr1-205064155-G-A
• rs1470637
• NM_005076.5:c.1241-167G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-205064155-G-A
• chr1-205064155-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005076.5(CNTN2):​c.1241-167G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 148,694 control chromosomes in the GnomAD database, including 14,468 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 (14468 hom., cov: 24)
• Consequence: CNTN2 NM_005076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN2	NM_005076.5	c.1241-167G>A		intron_variant	Intron 10 of 22	ENST00000331830.7	NP_005067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN2	ENST00000331830.7	c.1241-167G>A		intron_variant	Intron 10 of 22	1	NM_005076.5	ENSP00000330633.4

Frequencies

GnomAD3 genomes AF: 0.422 AC: 62704 AN: 148580 Hom.: 14455 Cov.: 24

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.422 AC: 62753 AN: 148694 Hom.: 14468 Cov.: 24 AF XY: 0.432 AC XY: 31257 AN XY: 72280

African (AFR) AF: 0.414 AC: 16691 AN: 40362

American (AMR) AF: 0.515 AC: 7631 AN: 14806

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1482 AN: 3440

East Asian (EAS) AF: 0.948 AC: 4622 AN: 4876

South Asian (SAS) AF: 0.733 AC: 3368 AN: 4596

European-Finnish (FIN) AF: 0.380 AC: 3773 AN: 9928

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23823 AN: 67442

Other (OTH) AF: 0.431 AC: 887 AN: 2056

Alfa AF: 0.375 Hom.: 18437

Bravo AF: 0.436

Asia WGS AF: 0.825 AC: 2865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.5
DANN	Benign	0.79
PhyloP100		0.049
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: rs1470637; hg19: chr1-205033283; COSMIC: COSV59349038; COSMIC: COSV59349038;