rs864309653

Variant names:

• chr12-88518757-TATGATGGAATAATTACT-A
• rs864309653
• NM_000899.5:c.286_303delAGTAATTATTCCATCATAinsT

Variant summary

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

The ENST00000644744.1(KITLG):​c.286_303delAGTAATTATTCCATCATAinsT​(p.Ser96fs) variant causes a frameshift, synonymous change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as no classifications from unflagged records (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KITLG ENST00000644744.1 frameshift, synonymous
• Clinical Significance: no classifications from unflagged records no classifications from unflagged records P:1
• Conservation: PhyloP100: 5.61
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 69

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• hyperpigmentation with or without hypopigmentation, familial progressive

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial progressive hyper- and hypopigmentation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial progressive hyperpigmentation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Waardenburg syndrome type 2

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• Waardenburg syndrome, IIa 2F

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000644744.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KITLG	NM_000899.5	MANE Select	c.286_303delAGTAATTATTCCATCATAinsT	p.Ser96fs	frameshift synonymous	Exon 4 of 10	NP_000890.1
	KITLG	NM_003994.6		c.286_303delAGTAATTATTCCATCATAinsT	p.Ser96fs	frameshift synonymous	Exon 4 of 9	NP_003985.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KITLG	ENST00000644744.1	MANE Select	c.286_303delAGTAATTATTCCATCATAinsT	p.Ser96fs	frameshift synonymous	Exon 4 of 10	ENSP00000495951.1
	KITLG	ENST00000347404.10	TSL:1	c.286_303delAGTAATTATTCCATCATAinsT	p.Ser96fs	frameshift synonymous	Exon 4 of 9	ENSP00000054216.5
	KITLG	ENST00000378535.4	TSL:1	n.229_246delAGTAATTATTCCATCATAinsT		non_coding_transcript_exon	Exon 3 of 9

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

ClinVar submissions as Germline

Significance: no classifications from unflagged records

Revision: no classifications from unflagged records

Pathogenic	VUS	Benign	Condition
1	-	-	Autosomal dominant nonsyndromic hearing loss 69 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.6
Mutation Taster		=2/198	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs864309653; hg19: chr12-88912534;