7-146347248-A-G

Position:

• chr7-146347248-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014141.6(CNTNAP2):​c.97+230275A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 152,072 control chromosomes in the GnomAD database, including 66,991 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 0.94 (66991 hom., cov: 30)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.696

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]

CNTNAP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.97+230275A>G		intron_variant		ENST00000361727.8	NP_054860.1
CNTNAP2	XM_017011950.3	c.97+230275A>G		intron_variant			XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.97+230275A>G		intron_variant		1	NM_014141.6	ENSP00000354778.3
CNTNAP2	ENST00000625365.2	c.97+230275A>G		intron_variant		5		ENSP00000485955.1
CNTNAP2	ENST00000637150.1	n.26+230275A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142505 AN: 151954 Hom.: 66929 Cov.: 30

Gnomad AFR AF: 0.983

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.987

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.938

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.938 AC: 142626 AN: 152072 Hom.: 66991 Cov.: 30 AF XY: 0.940 AC XY: 69858 AN XY: 74336

Gnomad4 AFR AF: 0.983

Gnomad4 AMR AF: 0.947

Gnomad4 ASJ AF: 0.917

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.987

Gnomad4 FIN AF: 0.923

Gnomad4 NFE AF: 0.904

Gnomad4 OTH AF: 0.938

Alfa AF: 0.919 Hom.: 31475

Bravo AF: 0.942

Asia WGS AF: 0.988 AC: 3433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs6972458; hg19: chr7-146044340;