chr2-8730732-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020738.4(KIDINS220):​c.5304A>G​(p.Glu1768Glu) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KIDINS220	NM_020738.4	c.5304A>G	p.Glu1768Glu	synonymous_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>G	p.Glu1768Glu	synonymous_variant	Exon 30 of 30	1	NM_020738.4	ENSP00000256707.4

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3791 AN: 152230 Hom.: 334 Cov.: 32

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

GnomAD2 exomes AF: 0.0514 AC: 12764 AN: 248314 AF XY: 0.0459

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 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.: 37 AF XY: 0.0191 AC XY: 13911 AN XY: 726488

Gnomad4 AFR exome AF: 0.00229 AC: 76 AN: 33250

Gnomad4 AMR exome AF: 0.151 AC: 6678 AN: 44352

Gnomad4 ASJ exome AF: 0.00353 AC: 92 AN: 26072

Gnomad4 EAS exome AF: 0.301 AC: 11946 AN: 39692

Gnomad4 SAS exome AF: 0.0504 AC: 4333 AN: 86056

Gnomad4 FIN exome AF: 0.0124 AC: 661 AN: 53348

Gnomad4 NFE exome AF: 0.00203 AC: 2256 AN: 1111494

Gnomad4 Remaining exome AF: 0.0279 AC: 1682 AN: 60280

GnomAD4 genome AF: 0.0251 AC: 3818 AN: 152348 Hom.: 344 Cov.: 32 AF XY: 0.0282 AC XY: 2100 AN XY: 74486

Gnomad4 AFR AF: 0.00365 AC: 0.00365472 AN: 0.00365472

Gnomad4 AMR AF: 0.0900 AC: 0.0899647 AN: 0.0899647

Gnomad4 ASJ AF: 0.00518 AC: 0.00518433 AN: 0.00518433

Gnomad4 EAS AF: 0.299 AC: 0.298879 AN: 0.298879

Gnomad4 SAS AF: 0.0620 AC: 0.0619561 AN: 0.0619561

Gnomad4 FIN AF: 0.0154 AC: 0.0154397 AN: 0.0154397

Gnomad4 NFE AF: 0.00263 AC: 0.00263104 AN: 0.00263104

Gnomad4 OTH AF: 0.0383 AC: 0.0382798 AN: 0.0382798

Alfa AF: 0.00599 Hom.: 21

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

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.97
DANN	Benign	0.46
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

Publications

LitVar

Other links and lift over

dbSNP: rs13406422; hg19: chr2-8870862; COSMIC: COSV56751556; COSMIC: COSV56751556;