20-43637268-CTT-C

Variant names:

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

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+26delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000838 in 1,037,990 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 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000084 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFT52 NM_016004.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT52	NM_016004.5	MANE Select	c.1120+25_1120+26delTT		intron	N/A	NP_057088.2
	IFT52	NM_001303458.3		c.1120+25_1120+26delTT		intron	N/A	NP_001290387.1
	IFT52	NM_001303459.3		c.1120+25_1120+26delTT		intron	N/A	NP_001290388.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT52	ENST00000373030.8	TSL:1 MANE Select	c.1120+16_1120+17delTT		intron	N/A	ENSP00000362121.3
	IFT52	ENST00000871354.1		c.1219+16_1219+17delTT		intron	N/A	ENSP00000541413.1
	IFT52	ENST00000871357.1		c.1219+16_1219+17delTT		intron	N/A	ENSP00000541416.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 147858 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000300 AC: 25 AN: 83288 AF XY: 0.000454

Gnomad AFR exome AF: 0.000273

Gnomad AMR exome AF: 0.000130

Gnomad ASJ exome AF: 0.00110

Gnomad EAS exome AF: 0.000298

Gnomad FIN exome AF: 0.000226

Gnomad NFE exome AF: 0.000280

Gnomad OTH exome AF: 0.000569

GnomAD4 exome AF: 0.0000838 AC: 87 AN: 1037990 Hom.: 0 AF XY: 0.0000992 AC XY: 51 AN XY: 514256

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

African (AFR) AF: 0.000267 AC: 6 AN: 22488

American (AMR) AF: 0.000262 AC: 6 AN: 22884

Ashkenazi Jewish (ASJ) AF: 0.0000629 AC: 1 AN: 15906

East Asian (EAS) AF: 0.0000686 AC: 2 AN: 29138

South Asian (SAS) AF: 0.000153 AC: 8 AN: 52240

European-Finnish (FIN) AF: 0.0000251 AC: 1 AN: 39792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4080

European-Non Finnish (NFE) AF: 0.0000717 AC: 58 AN: 808770

Other (OTH) AF: 0.000117 AC: 5 AN: 42692

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 147858 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 71992

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: 0.00 AC: 0 AN: 4684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9600

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66566

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

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: rs754046046; hg19: chr20-42265908;