2-124687887-G-A

Position:

• chr2-124687887-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001367498.1(CNTNAP5):​c.2077+39929G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 152,054 control chromosomes in the GnomAD database, including 46 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 0.023 (46 hom., cov: 32)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0231 (3505/152054) while in subpopulation NFE AF= 0.0318 (2163/67992). AF 95% confidence interval is 0.0307. There are 46 homozygotes in gnomad4. There are 1593 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTNAP5	NM_001367498.1	c.2077+39929G>A		intron_variant		ENST00000682447.1
CNTNAP5	NM_130773.4	c.2074+39929G>A		intron_variant
CNTNAP5	XM_017003316.2	c.2077+39929G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTNAP5	ENST00000682447.1	c.2077+39929G>A		intron_variant			NM_001367498.1	A1
CNTNAP5	ENST00000431078.1	c.2074+39929G>A		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3504 AN: 151940 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00767

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0318

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0231 AC: 3505 AN: 152054 Hom.: 46 Cov.: 32 AF XY: 0.0214 AC XY: 1593 AN XY: 74348

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.0531

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00788

Gnomad4 FIN AF: 0.0227

Gnomad4 NFE AF: 0.0318

Gnomad4 OTH AF: 0.0261

Alfa AF: 0.0255 Hom.: 4

Bravo AF: 0.0222

Asia WGS AF: 0.00434 AC: 15 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.36

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: rs10189889; hg19: chr2-125445464;