2-8808940-T-C

Position:

• chr2-8808940-T-C

Variant summary

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

The ENST00000256707.8(KIDINS220):​c.505-2571A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,100 control chromosomes in the GnomAD database, including 6,564 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 0.29 (6564 hom., cov: 33)
• Consequence: KIDINS220 ENST00000256707.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIDINS220	NM_020738.4	c.505-2571A>G		intron_variant		ENST00000256707.8	NP_065789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIDINS220	ENST00000256707.8	c.505-2571A>G		intron_variant		1	NM_020738.4	ENSP00000256707

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44076 AN: 151982 Hom.: 6565 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.290 AC: 44107 AN: 152100 Hom.: 6564 Cov.: 33 AF XY: 0.295 AC XY: 21903 AN XY: 74350

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.255

Alfa AF: 0.271 Hom.: 12788

Bravo AF: 0.285

Asia WGS AF: 0.249 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.53

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: rs7587928; hg19: chr2-8949070;