rs79431021

chr1-205064390-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2 BP4_Strong BP6_Moderate BA1

The NM_005076.5(CNTN2):c.1309C>G(p.Leu437Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,612,364 control chromosomes in the GnomAD database, including 530 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (173 hom., cov: 32)
  • Exomes 𝑓: 0.015 (357 hom.)
• Consequence: CNTN2 NM_005076.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.207

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 -13 ACMG points.

• PP2: Missense variant where missense usually causes diseases, CNTN2
• BP4: Computational evidence support a benign effect (MetaRNN=0.001802206).
• BP6: Variant 1-205064390-C-G is Benign according to our data. Variant chr1-205064390-C-G is described in ClinVar as [Benign]. Clinvar id is 474460.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN2	NM_005076.5	c.1309C>G	p.Leu437Val	missense_variant	11/23	ENST00000331830.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN2	ENST00000331830.7	c.1309C>G	p.Leu437Val	missense_variant	11/23	1	NM_005076.5	P1

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5305 AN: 152154 Hom.: 172 Cov.: 32

Gnomad AFR AF: 0.0894

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0237

Gnomad ASJ AF: 0.0654

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.0315

GnomAD3 exomes AF: 0.0179 AC: 4508 AN: 251172 Hom.: 120 AF XY: 0.0168 AC XY: 2276 AN XY: 135760

Gnomad AFR exome AF: 0.0941

Gnomad AMR exome AF: 0.0133

Gnomad ASJ exome AF: 0.0578

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00958

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.0131

Gnomad OTH exome AF: 0.0202

GnomAD4 exome AF: 0.0147 AC: 21517 AN: 1460092 Hom.: 357 Cov.: 32 AF XY: 0.0146 AC XY: 10571 AN XY: 725954

Gnomad4 AFR exome AF: 0.0958

Gnomad4 AMR exome AF: 0.0151

Gnomad4 ASJ exome AF: 0.0579

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0101

Gnomad4 FIN exome AF: 0.00180

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.0232

GnomAD4 genome AF: 0.0349 AC: 5320 AN: 152272 Hom.: 173 Cov.: 32 AF XY: 0.0338 AC XY: 2517 AN XY: 74450

Gnomad4 AFR AF: 0.0895

Gnomad4 AMR AF: 0.0238

Gnomad4 ASJ AF: 0.0654

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00622

Gnomad4 FIN AF: 0.00169

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0230 Hom.: 33

Bravo AF: 0.0410

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.0114 AC: 44

ESP6500AA AF: 0.0862 AC: 380

ESP6500EA AF: 0.0172 AC: 148

ExAC AF: 0.0190 AC: 2306

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.0157

EpiControl AF: 0.0171

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	0.0050
Dann	Benign	0.71
DEOGEN2	Benign	0.075	T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.020	N
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.83	N;N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.22	T
Polyphen		0.0	B;B;.
Vest4		0.030
MPC		0.42
ClinPred		0.00030	T
GERP RS		-7.0
Varity_R		0.024
gMVP		0.41

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: rs79431021; hg19: chr1-205033518;