rs10900443

Variant names:

• chr1-205075226-G-A
• rs10900443
• NM_005076.5:c.*1461G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005076.5(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 NM_005076.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 7 publications found

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]

CNTN2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• epilepsy, familial adult myoclonic, 5

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• benign adult familial myoclonic epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005076.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN2	NM_005076.5	MANE Select	c.*1461G>A		3_prime_UTR	Exon 23 of 23	NP_005067.1
	CNTN2	NR_144350.2		n.4794G>A		non_coding_transcript_exon	Exon 23 of 23
	CNTN2	NM_001346083.2		c.*1461G>A		3_prime_UTR	Exon 23 of 23	NP_001333012.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN2	ENST00000331830.7	TSL:1 MANE Select	c.*1461G>A		3_prime_UTR	Exon 23 of 23	ENSP00000330633.4
	CNTN2	ENST00000640326.1	TSL:5	n.*1277G>A		non_coding_transcript_exon	Exon 24 of 24	ENSP00000492495.1
	CNTN2	ENST00000636312.2	TSL:5	c.*1348G>A		3_prime_UTR	Exon 18 of 18	ENSP00000489754.2

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

African (AFR) AF: 0.658 AC: 2222 AN: 3378

American (AMR) AF: 0.921 AC: 2265 AN: 2458

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 3370 AN: 3952

East Asian (EAS) AF: 0.962 AC: 7506 AN: 7800

South Asian (SAS) AF: 0.906 AC: 750 AN: 828

European-Finnish (FIN) AF: 0.888 AC: 5057 AN: 5692

Middle Eastern (MID) AF: 0.821 AC: 440 AN: 536

European-Non Finnish (NFE) AF: 0.868 AC: 51174 AN: 58932

Other (OTH) AF: 0.854 AC: 5431 AN: 6358

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

African (AFR) AF: 0.643 AC: 26654 AN: 41432

American (AMR) AF: 0.885 AC: 13532 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2989 AN: 3466

East Asian (EAS) AF: 0.970 AC: 5015 AN: 5172

South Asian (SAS) AF: 0.913 AC: 4398 AN: 4818

European-Finnish (FIN) AF: 0.888 AC: 9411 AN: 10596

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58664 AN: 67984

Other (OTH) AF: 0.854 AC: 1807 AN: 2116

Alfa AF: 0.840 Hom.: 33465

Bravo AF: 0.808

Asia WGS AF: 0.932 AC: 3243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.087
DANN	Benign	0.67
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10900443; hg19: chr1-205044354;