2-8730732-T-A

Variant names:

• chr2-8730732-T-A
• rs13406422
• NM_020738.4:c.5304A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020738.4(KIDINS220):​c.5304A>T​(p.Glu1768Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: KIDINS220 NM_020738.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2928558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIDINS220	NM_020738.4	c.5304A>T	p.Glu1768Asp	missense_variant	Exon 30 of 30	ENST00000256707.8	NP_065789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIDINS220	ENST00000256707.8	c.5304A>T	p.Glu1768Asp	missense_variant	Exon 30 of 30	1	NM_020738.4	ENSP00000256707.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.97	D;D
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.0	N;N
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.18	T;T
Polyphen		0.79	P;.
Vest4		0.55
MutPred		0.085		Loss of helix (P = 0.1299);.;
MVP		0.43
MPC		0.44
ClinPred		0.66	D
GERP RS		-1.6
Varity_R		0.49
gMVP		0.29

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: rs13406422; hg19: chr2-8870862;