20-43637268-CTTT-CTTTTTT

Variant names:

• chr20-43637268-C-CTTT
• rs754046046
• NM_016004.5:c.1120+24_1120+26dupTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016004.5(IFT52):​c.1120+24_1120+26dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000192 in 1,040,488 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: IFT52 NM_016004.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 0 publications found

Genes affected

IFT52 (HGNC:15901): (intraflagellar transport 52) This gene encodes a conserved proline-rich protein that is a component of the intraflagellar transport-B (IFT-B) core complex. The encoded protein is essential for the integrity of the IFT-B core complex, and for biosynthesis and maintenance of cilia. Mutations in this gene are associated with ciliopathy that affects the skeleton. [provided by RefSeq, Oct 2016]

IFT52 Gene-Disease associations (from GenCC):

• short-rib thoracic dysplasia 16 with or without polydactyly

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• cranioectodermal dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016004.5. 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
	IFT52	NM_016004.5	MANE Select	c.1120+24_1120+26dupTTT		intron	N/A	NP_057088.2
	IFT52	NM_001303458.3		c.1120+24_1120+26dupTTT		intron	N/A	NP_001290387.1
	IFT52	NM_001303459.3		c.1120+24_1120+26dupTTT		intron	N/A	NP_001290388.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT52	ENST00000373030.8	TSL:1 MANE Select	c.1120+15_1120+16insTTT		intron	N/A	ENSP00000362121.3
	IFT52	ENST00000871354.1		c.1219+15_1219+16insTTT		intron	N/A	ENSP00000541413.1
	IFT52	ENST00000871357.1		c.1219+15_1219+16insTTT		intron	N/A	ENSP00000541416.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000192 AC: 2 AN: 1040488 Hom.: 0 Cov.: 15 AF XY: 0.00000194 AC XY: 1 AN XY: 515466

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22564

American (AMR) AF: 0.00 AC: 0 AN: 22952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15972

East Asian (EAS) AF: 0.00 AC: 0 AN: 29222

South Asian (SAS) AF: 0.00 AC: 0 AN: 52400

European-Finnish (FIN) AF: 0.0000251 AC: 1 AN: 39916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4086

European-Non Finnish (NFE) AF: 0.00000123 AC: 1 AN: 810582

Other (OTH) AF: 0.00 AC: 0 AN: 42794

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.088

Splicing

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

Other links and lift over

dbSNP: rs754046046; hg19: chr20-42265908;