1-205058200-G-T

Variant names:

• chr1-205058200-G-T
• NM_005076.5:c.235G>T

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_005076.5(CNTN2):​c.235G>T​(p.Glu79*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000698 in 1,432,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CNTN2 NM_005076.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.66

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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN2	NM_005076.5	c.235G>T	p.Glu79*	stop_gained	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.235G>T	p.Glu79*	stop_gained	Exon 4 of 23	1	NM_005076.5	ENSP00000330633.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432524 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 709674

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000416

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Pathogenic	0.78
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
Vest4		0.62
GERP RS		4.4

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-205027328;