Variant chr2-8730732-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020738.4(KIDINS220):c.5304A>G(p.Glu1768=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,612,648 control chromosomes in the GnomAD database, including 3,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 344 hom., cov: 32)

Exomes 𝑓: 0.019 ( 2679 hom. )

Consequence

KIDINS220
NM_020738.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0450

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 2-8730732-T-C is Benign according to our data. Variant chr2-8730732-T-C is described in ClinVar as [Benign]. Clinvar id is 1166247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.045 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIDINS220	NM_020738.4 linkuse as main transcript	c.5304A>G	p.Glu1768=	synonymous_variant	30/30	ENST00000256707.8	NP_065789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIDINS220	ENST00000256707.8 linkuse as main transcript	c.5304A>G	p.Glu1768=	synonymous_variant	30/30	1	NM_020738.4	ENSP00000256707		Q9ULH0-1

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3791

AN:

152230

Hom.:

334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00367

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0895

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.299

Gnomad SAS

AF:

0.0617

Gnomad FIN

AF:

0.0154

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00263

Gnomad OTH

AF:

0.0296

GnomAD3 exomes

AF:

0.0514

AC:

12764

AN:

248314

Hom.:

1201

AF XY:

0.0459

AC XY:

6189

AN XY:

134744

show subpopulations

Gnomad AFR exome

AF:

0.00362

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.00470

Gnomad EAS exome

AF:

0.274

Gnomad SAS exome

AF:

0.0498

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.00272

Gnomad OTH exome

AF:

0.0334

GnomAD4 exome

AF:

0.0190

AC:

27748

AN:

1460300

Hom.:

2679

Cov.:

AF XY:

0.0191

AC XY:

13911

AN XY:

726488

show subpopulations

Gnomad4 AFR exome

AF:

0.00229

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.00353

Gnomad4 EAS exome

AF:

0.301

Gnomad4 SAS exome

AF:

0.0504

Gnomad4 FIN exome

AF:

0.0124

Gnomad4 NFE exome

AF:

0.00203

Gnomad4 OTH exome

AF:

0.0279

GnomAD4 genome

AF:

0.0251

AC:

3818

AN:

152348

Hom.:

344

Cov.:

AF XY:

0.0282

AC XY:

2100

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00365

Gnomad4 AMR

AF:

0.0900

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.299

Gnomad4 SAS

AF:

0.0620

Gnomad4 FIN

AF:

0.0154

Gnomad4 NFE

AF:

0.00263

Gnomad4 OTH

AF:

0.0383

Alfa

AF:

0.00602

Hom.:

Bravo

AF:

0.0319

Asia WGS

AF:

0.174

AC:

605

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.97

DANN

Benign

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over