rs9787172

chr1-205058262-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005076.5(CNTN2):c.297C>T(p.Asn99=) 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:2
• Conservation: PhyloP100: 1.06

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 -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 id 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/exons	MANE	UniProt
CNTN2	NM_005076.5	c.297C>T	p.Asn99=	synonymous_variant	4/23	ENST00000331830.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN2	ENST00000331830.7	c.297C>T	p.Asn99=	synonymous_variant	4/23	1	NM_005076.5	P1

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

GnomAD3 exomes AF: 0.0468 AC: 9240 AN: 197604 Hom.: 358 AF XY: 0.0489 AC XY: 5116 AN XY: 104522

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 SAS exome AF: 0.129

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

Gnomad4 AFR exome AF: 0.0919

Gnomad4 AMR exome AF: 0.0237

Gnomad4 ASJ exome AF: 0.0648

Gnomad4 EAS exome AF: 0.0227

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.0806

Gnomad4 NFE exome AF: 0.0230

Gnomad4 OTH exome AF: 0.0392

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

Gnomad4 AFR AF: 0.0926

Gnomad4 AMR AF: 0.0339

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.0215

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0852

Gnomad4 NFE AF: 0.0243

Gnomad4 OTH AF: 0.0482

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 15, 2018

- -

Epilepsy, familial adult myoclonic, 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	9.5
Dann	Benign	0.78

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: rs9787172; hg19: chr1-205027390;