20-43637268-CTTT-CTTTTT

Variant names:

• chr20-43637268-C-CTT
• rs754046046
• NM_016004.5:c.1120+25_1120+26dupTT

Variant summary

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

The NM_016004.5(IFT52):​c.1120+25_1120+26dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,186,102 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: 𝑓 0.0000068 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (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 0 ACMG points.

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+25_1120+26dupTT		intron	N/A	NP_057088.2
	IFT52	NM_001303458.3		c.1120+25_1120+26dupTT		intron	N/A	NP_001290387.1
	IFT52	NM_001303459.3		c.1120+25_1120+26dupTT		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+16insTT		intron	N/A	ENSP00000362121.3
	IFT52	ENST00000871354.1		c.1219+15_1219+16insTT		intron	N/A	ENSP00000541413.1
	IFT52	ENST00000871357.1		c.1219+15_1219+16insTT		intron	N/A	ENSP00000541416.1

Frequencies

GnomAD3 genomes AF: 0.00000676 AC: 1 AN: 147866 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000276 AC: 23 AN: 83288 AF XY: 0.000227

Gnomad AFR exome AF: 0.000137

Gnomad AMR exome AF: 0.000130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000298

Gnomad FIN exome AF: 0.000679

Gnomad NFE exome AF: 0.000233

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000146 AC: 152 AN: 1038236 Hom.: 0 Cov.: 15 AF XY: 0.000161 AC XY: 83 AN XY: 514366

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

African (AFR) AF: 0.0000444 AC: 1 AN: 22500

American (AMR) AF: 0.000131 AC: 3 AN: 22898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15924

East Asian (EAS) AF: 0.000172 AC: 5 AN: 29146

South Asian (SAS) AF: 0.0000765 AC: 4 AN: 52284

European-Finnish (FIN) AF: 0.000477 AC: 19 AN: 39828

Middle Eastern (MID) AF: 0.000245 AC: 1 AN: 4074

European-Non Finnish (NFE) AF: 0.000135 AC: 109 AN: 808906

Other (OTH) AF: 0.000234 AC: 10 AN: 42676

⚠️ 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 AF: 0.00000676 AC: 1 AN: 147866 Hom.: 0 Cov.: 33 AF XY: 0.0000139 AC XY: 1 AN XY: 71996

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

African (AFR) AF: 0.00 AC: 0 AN: 40540

American (AMR) AF: 0.00 AC: 0 AN: 14740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.00 AC: 0 AN: 5100

South Asian (SAS) AF: 0.000213 AC: 1 AN: 4684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66568

Other (OTH) AF: 0.00 AC: 0 AN: 2026

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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;