rs7587928

Variant names:

• chr2-8808940-T-C
• rs7587928
• NM_020738.4:c.505-2571A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

KIDINS220 Gene-Disease associations (from GenCC):

• spastic paraplegia, intellectual disability, nystagmus, and obesity

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• ventriculomegaly and arthrogryposis

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000256707.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIDINS220	NM_020738.4	MANE Select	c.505-2571A>G		intron	N/A	NP_065789.1
	KIDINS220	NM_001348729.2		c.508-2571A>G		intron	N/A	NP_001335658.1
	KIDINS220	NM_001348731.2		c.508-2571A>G		intron	N/A	NP_001335660.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIDINS220	ENST00000256707.8	TSL:1 MANE Select	c.505-2571A>G		intron	N/A	ENSP00000256707.4
	KIDINS220	ENST00000319688.5	TSL:1	c.508-2571A>G		intron	N/A	ENSP00000319947.5
	KIDINS220	ENST00000488729.5	TSL:1	n.*565-2571A>G		intron	N/A	ENSP00000417390.1

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

African (AFR) AF: 0.320 AC: 13270 AN: 41464

American (AMR) AF: 0.263 AC: 4013 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3472

East Asian (EAS) AF: 0.203 AC: 1053 AN: 5176

South Asian (SAS) AF: 0.269 AC: 1296 AN: 4820

European-Finnish (FIN) AF: 0.382 AC: 4033 AN: 10562

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18605 AN: 68002

Other (OTH) AF: 0.255 AC: 539 AN: 2114

Alfa AF: 0.274 Hom.: 25737

Bravo AF: 0.285

Asia WGS AF: 0.249 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7587928; hg19: chr2-8949070;