Genetic Variant KIDINS220:p.Ter1349Serext*? (chr2-8726894-T-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4

The NM_001348738.2(KIDINS220):c.4046A>C(p.Ter1349Serext*?) variant causes a stop lost 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. Synonymous variant affecting the same amino acid position has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

KIDINS220
NM_001348738.2 stop_lost

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

ventriculomegaly and arthrogryposis
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
spastic paraplegia, intellectual disability, nystagmus, and obesity
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

KIDINS220 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Stoplost variant in NM_001348738.2 Downstream stopcodon found after 1526 codons.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348738.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIDINS220	NM_001348738.2	c.4046A>C	p.Ter1349Serext*?	stop_lost	Exon 29 of 30	NP_001335667.1
KIDINS220	NM_001348739.2	c.3935A>C	p.Ter1312Serext*?	stop_lost	Exon 28 of 29	NP_001335668.1
KIDINS220	NM_001348740.2	c.3935A>C	p.Ter1312Serext*?	stop_lost	Exon 28 of 29	NP_001335669.1

Ensembl Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIDINS220	ENST00000689852.1	c.3965A>C	p.Ter1322Serext*?	stop_lost	Exon 29 of 30	ENSP00000510537.1	A0A8I5QL22
KIDINS220	ENST00000689369.1	c.3932A>C	p.Ter1311Serext*?	stop_lost	Exon 28 of 29	ENSP00000509856.1	A0A8I5QJC0
KIDINS220	ENST00000693394.1	c.3932A>C	p.Ter1311Serext*?	stop_lost	Exon 28 of 29	ENSP00000509014.1	A0A8I5QJC0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000743

AC:

AN:

134542

AF XY:

0.0000136

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000121

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.69

Eigen

Benign

0.018

Eigen_PC

Benign

0.043

FATHMM_MKL

Uncertain

0.85

PhyloP100

1.2

GERP RS

3.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over