rs17722392

Variant names:

• chr2-8800024-A-C
• rs17722392
• NM_020738.4:c.900+376T>G

Variant summary

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

The NM_020738.4(KIDINS220):​c.900+376T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 152,318 control chromosomes in the GnomAD database, including 226 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 0.049 (226 hom., cov: 32)
• Consequence: KIDINS220 NM_020738.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146

Genes affected

KIDINS220 (HGNC:29508): (kinase D interacting substrate 220) This gene encodes a transmembrane protein that is preferentially expressed in the nervous system where it controls neuronal cell survival, differentiation into exons and dendrites, and synaptic plasticity. The encoded protein interacts with membrane receptors, cytosolic signaling components, and cytoskeletal proteins, serving as a scaffold that mediates crosstalk between the neurotrophin pathway and several other intracellular signaling pathways. Aberrant expression of this gene is associated with the onset of various neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease. Naturally occurring mutations in this gene are associated with a syndrome characterized by spastic paraplegia, intellectual disability, nystagmus and obesity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIDINS220	NM_020738.4	c.900+376T>G		intron_variant	Intron 9 of 29	ENST00000256707.8	NP_065789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIDINS220	ENST00000256707.8	c.900+376T>G		intron_variant	Intron 9 of 29	1	NM_020738.4	ENSP00000256707.4

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7437 AN: 152200 Hom.: 226 Cov.: 32

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.0672

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.0636

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

GnomAD4 genome AF: 0.0488 AC: 7434 AN: 152318 Hom.: 226 Cov.: 32 AF XY: 0.0479 AC XY: 3571 AN XY: 74492

Gnomad4 AFR AF: 0.0125

Gnomad4 AMR AF: 0.0672

Gnomad4 ASJ AF: 0.0807

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.0418

Gnomad4 NFE AF: 0.0694

Gnomad4 OTH AF: 0.0625

Alfa AF: 0.0606 Hom.: 204

Bravo AF: 0.0504

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.45

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: rs17722392; hg19: chr2-8940154;