rs9787172

Variant names:

• chr1-205058262-C-T
• rs9787172
• NM_005076.5:c.297C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005076.5(CNTN2):​c.297C>T​(p.Asn99Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,548,416 control chromosomes in the GnomAD database, including 1,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (328 hom., cov: 32)
  • Exomes 𝑓: 0.033 (1376 hom.)
• Consequence: CNTN2 NM_005076.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.06
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 1-205058262-C-T is Benign according to our data. Variant chr1-205058262-C-T is described in ClinVar as Benign. ClinVar VariationId is 474482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN2	NM_005076.5	c.297C>T	p.Asn99Asn	synonymous_variant	Exon 4 of 23	ENST00000331830.7	NP_005067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN2	ENST00000331830.7	c.297C>T	p.Asn99Asn	synonymous_variant	Exon 4 of 23	1	NM_005076.5	ENSP00000330633.4

Frequencies

GnomAD3 genomes AF: 0.0523 AC: 7959 AN: 152070 Hom.: 322 Cov.: 32

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.0440

GnomAD2 exomes AF: 0.0468 AC: 9240 AN: 197604 AF XY: 0.0489

Gnomad AFR exome AF: 0.0960

Gnomad AMR exome AF: 0.0220

Gnomad ASJ exome AF: 0.0662

Gnomad EAS exome AF: 0.0158

Gnomad FIN exome AF: 0.0832

Gnomad NFE exome AF: 0.0270

Gnomad OTH exome AF: 0.0406

GnomAD4 exome AF: 0.0332 AC: 46419 AN: 1396228 Hom.: 1376 Cov.: 32 AF XY: 0.0355 AC XY: 24375 AN XY: 687328

African (AFR) AF: 0.0919 AC: 2894 AN: 31488

American (AMR) AF: 0.0237 AC: 857 AN: 36142

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 1394 AN: 21518

East Asian (EAS) AF: 0.0227 AC: 890 AN: 39160

South Asian (SAS) AF: 0.120 AC: 8979 AN: 74568

European-Finnish (FIN) AF: 0.0806 AC: 4072 AN: 50552

Middle Eastern (MID) AF: 0.0429 AC: 233 AN: 5434

European-Non Finnish (NFE) AF: 0.0230 AC: 24847 AN: 1079956

Other (OTH) AF: 0.0392 AC: 2253 AN: 57410

GnomAD4 genome AF: 0.0524 AC: 7981 AN: 152188 Hom.: 328 Cov.: 32 AF XY: 0.0554 AC XY: 4125 AN XY: 74420

African (AFR) AF: 0.0926 AC: 3846 AN: 41514

American (AMR) AF: 0.0339 AC: 519 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 233 AN: 3470

East Asian (EAS) AF: 0.0215 AC: 111 AN: 5168

South Asian (SAS) AF: 0.124 AC: 596 AN: 4806

European-Finnish (FIN) AF: 0.0852 AC: 904 AN: 10608

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0243 AC: 1651 AN: 67998

Other (OTH) AF: 0.0482 AC: 102 AN: 2114

Alfa AF: 0.0415 Hom.: 79

Bravo AF: 0.0477

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Oct 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Epilepsy, familial adult myoclonic, 5 Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.5
DANN	Benign	0.78
PhyloP100		1.1
Mutation Taster		=98/2	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: rs9787172; hg19: chr1-205027390;