1-205075288-C-A

Position:

• chr1-205075288-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005076.5(CNTN2):​c.*1523C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 163,738 control chromosomes in the GnomAD database, including 67,811 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 0.91 (63322 hom., cov: 31)
  • Exomes 𝑓: 0.88 (4489 hom.)
• Consequence: CNTN2 NM_005076.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN2	NM_005076.5	c.*1523C>A		3_prime_UTR_variant	23/23	ENST00000331830.7	NP_005067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN2	ENST00000331830.7	c.*1523C>A		3_prime_UTR_variant	23/23	1	NM_005076.5	ENSP00000330633	P1
CNTN2	ENST00000636312.2	c.*1410C>A		3_prime_UTR_variant	18/18	5		ENSP00000489754
CNTN2	ENST00000640326.1	c.*1339C>A		3_prime_UTR_variant, NMD_transcript_variant	24/24	5		ENSP00000492495

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138545 AN: 152074 Hom.: 63262 Cov.: 31

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.927

GnomAD4 exome AF: 0.882 AC: 10182 AN: 11546 Hom.: 4489 Cov.: 0 AF XY: 0.885 AC XY: 5171 AN XY: 5840

Gnomad4 AFR exome AF: 0.972

Gnomad4 AMR exome AF: 0.951

Gnomad4 ASJ exome AF: 0.864

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.867

Gnomad4 FIN exome AF: 0.874

Gnomad4 NFE exome AF: 0.866

Gnomad4 OTH exome AF: 0.891

GnomAD4 genome AF: 0.911 AC: 138665 AN: 152192 Hom.: 63322 Cov.: 31 AF XY: 0.912 AC XY: 67836 AN XY: 74406

Gnomad4 AFR AF: 0.978

Gnomad4 AMR AF: 0.922

Gnomad4 ASJ AF: 0.878

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.889

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.929

Alfa AF: 0.888 Hom.: 18530

Bravo AF: 0.919

Asia WGS AF: 0.969 AC: 3369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.65

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: rs10900444; hg19: chr1-205044416;