rs10900444

Variant names:

• chr1-205075288-C-A
• rs10900444
• NM_005076.5:c.*1523C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-205075288-C-A
• chr1-205075288-C-G
• chr1-205075288-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.91).
• 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 rank	MANE	Protein	UniProt
CNTN2	NM_005076.5	c.*1523C>A		3_prime_UTR_variant	Exon 23 of 23	ENST00000331830.7	NP_005067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN2	ENST00000331830.7	c.*1523C>A		3_prime_UTR_variant	Exon 23 of 23	1	NM_005076.5	ENSP00000330633.4

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

African (AFR) AF: 0.972 AC: 494 AN: 508

American (AMR) AF: 0.951 AC: 272 AN: 286

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 463 AN: 536

East Asian (EAS) AF: 0.998 AC: 665 AN: 666

South Asian (SAS) AF: 0.867 AC: 85 AN: 98

European-Finnish (FIN) AF: 0.874 AC: 570 AN: 652

Middle Eastern (MID) AF: 0.743 AC: 52 AN: 70

European-Non Finnish (NFE) AF: 0.866 AC: 6845 AN: 7904

Other (OTH) AF: 0.891 AC: 736 AN: 826

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

African (AFR) AF: 0.978 AC: 40601 AN: 41510

American (AMR) AF: 0.922 AC: 14103 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3047 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5158 AN: 5162

South Asian (SAS) AF: 0.914 AC: 4415 AN: 4828

European-Finnish (FIN) AF: 0.889 AC: 9425 AN: 10606

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.865 AC: 58842 AN: 68002

Other (OTH) AF: 0.929 AC: 1961 AN: 2112

Alfa AF: 0.890 Hom.: 23175

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
PhyloP100		-1.2
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: rs10900444; hg19: chr1-205044416;