7-146116214-TGGCGGC-T

Position:

• chr7-146116214-TGGCGGC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000625365.2(CNTNAP2):​c.-230+126_-230+131delGGCGGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 151,762 control chromosomes in the GnomAD database, including 75,094 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (74872 hom., cov: 0)
  • Exomes 𝑓: 0.80 (222 hom.)
• Consequence: CNTNAP2 ENST00000625365.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.69

Genes affected

CNTNAP2 (HGNC:13830): (contactin associated protein 2) This gene encodes a member of the neurexin family which functions 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, thrombospondin N-terminal-like domains and a putative PDZ binding site. This protein is localized at the juxtaparanodes of myelinated axons, and mediates interactions between neurons and glia during nervous system development and is also involved in localization of potassium channels within differentiating axons. This gene encompasses almost 1.5% of chromosome 7 and is one of the largest genes in the human genome. It is directly bound and regulated by forkhead box protein P2, a transcription factor related to speech and language development. This gene has been implicated in multiple neurodevelopmental disorders, including Gilles de la Tourette syndrome, schizophrenia, epilepsy, autism, ADHD and intellectual disability. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-146116214-TGGCGGC-T is Benign according to our data. Variant chr7-146116214-TGGCGGC-T is described in ClinVar as [Benign]. Clinvar id is 1263242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000625365.2	c.-230+126_-230+131delGGCGGC		intron_variant		5		ENSP00000485955.1

Frequencies

GnomAD3 genomes AF: 0.995 AC: 150350 AN: 151068 Hom.: 74820 Cov.: 0

Gnomad AFR AF: 0.998

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.997

Gnomad FIN AF: 0.999

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.997

GnomAD4 exome AF: 0.796 AC: 468 AN: 588 Hom.: 222 AF XY: 0.774 AC XY: 325 AN XY: 420

Gnomad4 AFR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.833

Gnomad4 EAS exome AF: 0.588

Gnomad4 SAS exome AF: 0.939

Gnomad4 NFE exome AF: 0.766

Gnomad4 OTH exome AF: 0.962

GnomAD4 genome AF: 0.995 AC: 150455 AN: 151174 Hom.: 74872 Cov.: 0 AF XY: 0.996 AC XY: 73522 AN XY: 73852

Gnomad4 AFR AF: 0.998

Gnomad4 AMR AF: 0.997

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.997

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.993

Gnomad4 OTH AF: 0.997

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145880908; hg19: chr7-145813306;