12-88518857-CAAT-C

Position:

• chr12-88518857-CAAT-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PM4_Supporting PP5

The NM_000899.5(KITLG):​c.200_202delATT​(p.His67_Cys68delinsArg) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KITLG NM_000899.5 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.60

Genes affected

KITLG (HGNC:6343): (KIT ligand) This gene encodes the ligand of the tyrosine-kinase receptor encoded by the KIT locus. This ligand is a pleiotropic factor that acts in utero in germ cell and neural cell development, and hematopoiesis, all believed to reflect a role in cell migration. In adults, it functions pleiotropically, while mostly noted for its continued requirement in hematopoiesis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

KITLG (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a disulfide_bond (size 85) in uniprot entity SCF_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_000899.5
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000899.5. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 12-88518857-CAAT-C is Pathogenic according to our data. Variant chr12-88518857-CAAT-C is described in ClinVar as [Pathogenic]. Clinvar id is 218888.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-88518857-CAAT-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KITLG	NM_000899.5	c.200_202delATT	p.His67_Cys68delinsArg	disruptive_inframe_deletion	4/10	ENST00000644744.1	NP_000890.1
KITLG	NM_003994.6	c.200_202delATT	p.His67_Cys68delinsArg	disruptive_inframe_deletion	4/9		NP_003985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1	c.200_202delATT	p.His67_Cys68delinsArg	disruptive_inframe_deletion	4/10		NM_000899.5	ENSP00000495951.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 69 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 05, 2015

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs864309654; hg19: chr12-88912634;