rs2291101

Variant names:

• chr3-1383034-G-A
• rs2291101
• NM_001289080.2:c.2259G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-1383034-G-A
• chr3-1383034-G-C
• chr3-1383034-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001289080.2(CNTN6):​c.2259G>A​(p.Val753Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,613,376 control chromosomes in the GnomAD database, including 155,730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13691 hom., cov: 32)
  • Exomes 𝑓: 0.44 (142039 hom.)
• Consequence: CNTN6 NM_001289080.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.27
• Publications: 18 publications found

Genes affected

CNTN6 (HGNC:2176): (contactin 6) The protein encoded by this gene is a member of the immunoglobulin superfamily. It is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

CNTN6 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-1383034-G-A is Benign according to our data. Variant chr3-1383034-G-A is described in ClinVar as Benign. ClinVar VariationId is 402550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN6	NM_001289080.2	c.2259G>A	p.Val753Val	synonymous_variant	Exon 18 of 23	ENST00000446702.7	NP_001276009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN6	ENST00000446702.7	c.2259G>A	p.Val753Val	synonymous_variant	Exon 18 of 23	1	NM_001289080.2	ENSP00000407822.2
CNTN6	ENST00000350110.2	c.2259G>A	p.Val753Val	synonymous_variant	Exon 18 of 23	1		ENSP00000341882.2
CNTN6	ENST00000397479.6	n.*2397G>A		non_coding_transcript_exon_variant	Exon 17 of 22	2		ENSP00000380616.2
CNTN6	ENST00000397479.6	n.*2397G>A		3_prime_UTR_variant	Exon 17 of 22	2		ENSP00000380616.2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63444 AN: 151888 Hom.: 13675 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.418

GnomAD2 exomes AF: 0.450 AC: 113114 AN: 251386 AF XY: 0.450

Gnomad AFR exome AF: 0.373

Gnomad AMR exome AF: 0.536

Gnomad ASJ exome AF: 0.403

Gnomad EAS exome AF: 0.641

Gnomad FIN exome AF: 0.301

Gnomad NFE exome AF: 0.418

Gnomad OTH exome AF: 0.433

GnomAD4 exome AF: 0.437 AC: 638619 AN: 1461370 Hom.: 142039 Cov.: 40 AF XY: 0.438 AC XY: 318707 AN XY: 727024

African (AFR) AF: 0.368 AC: 12319 AN: 33454

American (AMR) AF: 0.535 AC: 23900 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 10508 AN: 26120

East Asian (EAS) AF: 0.627 AC: 24879 AN: 39694

South Asian (SAS) AF: 0.521 AC: 44949 AN: 86254

European-Finnish (FIN) AF: 0.302 AC: 16131 AN: 53418

Middle Eastern (MID) AF: 0.487 AC: 2811 AN: 5768

European-Non Finnish (NFE) AF: 0.428 AC: 476289 AN: 1111596

Other (OTH) AF: 0.444 AC: 26833 AN: 60386

GnomAD4 genome AF: 0.418 AC: 63511 AN: 152006 Hom.: 13691 Cov.: 32 AF XY: 0.418 AC XY: 31042 AN XY: 74286

African (AFR) AF: 0.375 AC: 15524 AN: 41452

American (AMR) AF: 0.502 AC: 7672 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1433 AN: 3464

East Asian (EAS) AF: 0.641 AC: 3311 AN: 5162

South Asian (SAS) AF: 0.518 AC: 2496 AN: 4822

European-Finnish (FIN) AF: 0.291 AC: 3068 AN: 10558

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28594 AN: 67966

Other (OTH) AF: 0.418 AC: 881 AN: 2108

Alfa AF: 0.415 Hom.: 7385

Bravo AF: 0.429

Asia WGS AF: 0.548 AC: 1900 AN: 3478

EpiCase AF: 0.426

EpiControl AF: 0.431

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.36
DANN	Benign	0.60
PhyloP100		-1.3
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: rs2291101; hg19: chr3-1424718; COSMIC: COSV63173618;