2-124242303-C-T

Variant names:

• chr2-124242303-C-T
• rs369801109
• NM_001367498.1:c.291C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_001367498.1(CNTNAP5):​c.291C>T​(p.Tyr97Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,612,630 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: CNTNAP5 NM_001367498.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.685
• Publications: 2 publications found

Genes affected

CNTNAP5 (HGNC:18748): (contactin associated protein family member 5) This gene product belongs to the neurexin family, members of which function in the vertebrate nervous system as cell adhesion molecules and receptors. This protein, like other neurexin proteins, contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, and thrombospondin N-terminal-like domains. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 2-124242303-C-T is Benign according to our data. Variant chr2-124242303-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 710619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.685 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1	c.291C>T	p.Tyr97Tyr	synonymous_variant	Exon 3 of 24	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4	c.291C>T	p.Tyr97Tyr	synonymous_variant	Exon 3 of 24		NP_570129.1
CNTNAP5	XM_017003316.2	c.291C>T	p.Tyr97Tyr	synonymous_variant	Exon 3 of 23		XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1	c.291C>T	p.Tyr97Tyr	synonymous_variant	Exon 3 of 24		NM_001367498.1	ENSP00000508115.1
CNTNAP5	ENST00000431078.1	c.291C>T	p.Tyr97Tyr	synonymous_variant	Exon 3 of 24	1		ENSP00000399013.1
CNTNAP5	ENST00000470921.1	n.209C>T		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152074 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000239 AC: 59 AN: 247016 AF XY: 0.000246

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000292

Gnomad ASJ exome AF: 0.000300

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000339

Gnomad OTH exome AF: 0.000334

GnomAD4 exome AF: 0.000210 AC: 307 AN: 1460556 Hom.: 1 Cov.: 31 AF XY: 0.000227 AC XY: 165 AN XY: 726480

African (AFR) AF: 0.000239 AC: 8 AN: 33454

American (AMR) AF: 0.000427 AC: 19 AN: 44528

Ashkenazi Jewish (ASJ) AF: 0.000192 AC: 5 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39492

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86062

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53358

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5764

European-Non Finnish (NFE) AF: 0.000179 AC: 199 AN: 1111460

Other (OTH) AF: 0.000464 AC: 28 AN: 60332

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152074 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74280

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.000328 AC: 5 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00316 AC: 1 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67992

Other (OTH) AF: 0.00144 AC: 3 AN: 2090

Alfa AF: 0.000294 Hom.: 0

Bravo AF: 0.000212

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CNTNAP5-related disorder Benign:1

Mar 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	3.0
DANN	Benign	0.67
PhyloP100		-0.69
Mutation Taster		=87/13	polymorphism

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: rs369801109; hg19: chr2-124999880; COSMIC: COSV70477419;