12-88532513-CAAAA-CAAAAA

Variant names:

• chr12-88532513-C-CA
• rs11428619
• NM_000899.5:c.130-11dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000899.5(KITLG):​c.130-11dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,239,402 control chromosomes in the GnomAD database, including 2,098 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (601 hom., cov: 30)
  • Exomes 𝑓: 0.14 (1497 hom.)
• Consequence: KITLG NM_000899.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.318
• Publications: 3 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 12-88532513-C-CA is Benign according to our data. Variant chr12-88532513-C-CA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 517646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000899.5. 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
	KITLG	NM_000899.5	MANE Select	c.130-11dupT		intron	N/A	NP_000890.1
	KITLG	NM_003994.6		c.130-11dupT		intron	N/A	NP_003985.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KITLG	ENST00000644744.1	MANE Select	c.130-11_130-10insT		intron	N/A	ENSP00000495951.1
	KITLG	ENST00000347404.10	TSL:1	c.130-11_130-10insT		intron	N/A	ENSP00000054216.5
	KITLG	ENST00000378535.4	TSL:1	n.73-11_73-10insT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0944 AC: 13312 AN: 141008 Hom.: 600 Cov.: 30

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.0752

Gnomad AMR AF: 0.0835

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0974

Gnomad MID AF: 0.0690

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.110

GnomAD2 exomes AF: 0.165 AC: 19607 AN: 118740 AF XY: 0.172

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.0296

Gnomad FIN exome AF: 0.160

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.136 AC: 148939 AN: 1098342 Hom.: 1497 Cov.: 23 AF XY: 0.137 AC XY: 74407 AN XY: 543938

African (AFR) AF: 0.110 AC: 2636 AN: 24048

American (AMR) AF: 0.0931 AC: 2804 AN: 30108

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 1852 AN: 17778

East Asian (EAS) AF: 0.0545 AC: 1435 AN: 26328

South Asian (SAS) AF: 0.143 AC: 8673 AN: 60798

European-Finnish (FIN) AF: 0.116 AC: 4419 AN: 38184

Middle Eastern (MID) AF: 0.114 AC: 484 AN: 4248

European-Non Finnish (NFE) AF: 0.142 AC: 120799 AN: 852638

Other (OTH) AF: 0.132 AC: 5837 AN: 44212

GnomAD4 genome AF: 0.0944 AC: 13315 AN: 141060 Hom.: 601 Cov.: 30 AF XY: 0.0929 AC XY: 6353 AN XY: 68370

African (AFR) AF: 0.0838 AC: 3208 AN: 38290

American (AMR) AF: 0.0834 AC: 1173 AN: 14068

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 220 AN: 3316

East Asian (EAS) AF: 0.0116 AC: 56 AN: 4838

South Asian (SAS) AF: 0.103 AC: 464 AN: 4492

European-Finnish (FIN) AF: 0.0974 AC: 831 AN: 8528

Middle Eastern (MID) AF: 0.0746 AC: 20 AN: 268

European-Non Finnish (NFE) AF: 0.110 AC: 7067 AN: 64446

Other (OTH) AF: 0.108 AC: 211 AN: 1950

Alfa AF: 0.0614 Hom.: 31

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hyperpigmentation with or without hypopigmentation, familial progressive;C2674081:SKIN/HAIR/EYE PIGMENTATION 7, DARK/LIGHT SKIN;C4225241:Autosomal dominant nonsyndromic hearing loss 69 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
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: rs11428619; hg19: chr12-88926290;