rs10900443

Positions:

• chr1-205075226-G-A

Variant summary

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

The ENST00000331830.7(CNTN2):​c.*1461G>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 0.834 in 242,010 control chromosomes in the GnomAD database, including 85,170 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 0.81 (51056 hom., cov: 31)
  • Exomes 𝑓: 0.87 (34114 hom.)
• Consequence: CNTN2 ENST00000331830.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN2	NM_005076.5	c.*1461G>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.*1461G>A		3_prime_UTR_variant	23/23	1	NM_005076.5	ENSP00000330633	P1
CNTN2	ENST00000636312.2	c.*1348G>A		3_prime_UTR_variant	18/18	5		ENSP00000489754
CNTN2	ENST00000640326.1	c.*1277G>A		3_prime_UTR_variant, NMD_transcript_variant	24/24	5		ENSP00000492495
CNTN2	ENST00000639788.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123510 AN: 151958 Hom.: 51036 Cov.: 31

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.852

GnomAD4 exome AF: 0.870 AC: 78215 AN: 89934 Hom.: 34114 Cov.: 0 AF XY: 0.871 AC XY: 39087 AN XY: 44856

Gnomad4 AFR exome AF: 0.658

Gnomad4 AMR exome AF: 0.921

Gnomad4 ASJ exome AF: 0.853

Gnomad4 EAS exome AF: 0.962

Gnomad4 SAS exome AF: 0.906

Gnomad4 FIN exome AF: 0.888

Gnomad4 NFE exome AF: 0.868

Gnomad4 OTH exome AF: 0.854

GnomAD4 genome AF: 0.813 AC: 123572 AN: 152076 Hom.: 51056 Cov.: 31 AF XY: 0.816 AC XY: 60690 AN XY: 74350

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.885

Gnomad4 ASJ AF: 0.862

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.913

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.854

Alfa AF: 0.840 Hom.: 21890

Bravo AF: 0.808

Asia WGS AF: 0.932 AC: 3243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.087
DANN	Benign	0.67

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: rs10900443; hg19: chr1-205044354;