12-64203799-C-T

Variant names:

• chr12-64203799-C-T
• rs1695105
• NM_152440.5:c.522-9141G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152440.5(KICS2):​c.522-9141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,082 control chromosomes in the GnomAD database, including 17,591 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 0.48 (17591 hom., cov: 33)
• Consequence: KICS2 NM_152440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 5 publications found

Genes affected

KICS2 (HGNC:26517): (KICSTOR subunit 2) Involved in cellular response to starvation; negative regulation of TORC1 signaling; and protein localization to lysosome. Located in intercellular bridge and lysosome. Part of KICSTOR complex. [provided by Alliance of Genome Resources, Apr 2022]

KICS2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152440.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KICS2	NM_152440.5	MANE Select	c.522-9141G>A		intron	N/A	NP_689653.4
	KICS2	NM_001300940.2		c.522-9141G>A		intron	N/A	NP_001287869.2	J3KNH0
	KICS2	NM_001300941.2		c.363-9141G>A		intron	N/A	NP_001287870.2	F5H2Q3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KICS2	ENST00000398055.8	TSL:1 MANE Select	c.522-9141G>A		intron	N/A	ENSP00000381132.4	Q96MD2
	KICS2	ENST00000311915.12	TSL:1	c.522-9141G>A		intron	N/A	ENSP00000311486.8	J3KNH0
	KICS2	ENST00000907624.1		c.522-9141G>A		intron	N/A	ENSP00000577683.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72599 AN: 151966 Hom.: 17586 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.498

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.478 AC: 72628 AN: 152082 Hom.: 17591 Cov.: 33 AF XY: 0.476 AC XY: 35362 AN XY: 74332

African (AFR) AF: 0.402 AC: 16685 AN: 41478

American (AMR) AF: 0.514 AC: 7852 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1765 AN: 3464

East Asian (EAS) AF: 0.478 AC: 2470 AN: 5168

South Asian (SAS) AF: 0.434 AC: 2093 AN: 4824

European-Finnish (FIN) AF: 0.460 AC: 4865 AN: 10566

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35223 AN: 67990

Other (OTH) AF: 0.500 AC: 1055 AN: 2108

Alfa AF: 0.494 Hom.: 2976

Bravo AF: 0.479

Asia WGS AF: 0.510 AC: 1776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.72
PhyloP100		0.32
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: rs1695105; hg19: chr12-64597579; COSMIC: COSV108143431; COSMIC: COSV108143431;