NM_015662.3:c.1390_1395delGATATT

Variant names:

• chr2-27476656-TAATATC-T
• rs587777084
• NM_015662.3:c.1390_1395delGATATT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM4 PP5

The NM_015662.3(IFT172):​c.1390_1395delGATATT​(p.Asp464_Ile465del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00000419 in 1,433,614 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: IFT172 NM_015662.3 conservative_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.18
• Publications: 0 publications found

Genes affected

IFT172 (HGNC:30391): (intraflagellar transport 172) This gene encodes a subunit of the intraflagellar transport subcomplex IFT-B. Subcomplexes IFT-A and IFT-B are necessary for ciliary assembly and maintenance. Mutations in this gene have been associated with skeletal ciliopathies, with or without polydactyly, such as such short-rib thoracic dysplasias 1, 9 or 10. [provided by RefSeq, Mar 2014]

IFT172 Gene-Disease associations (from GenCC):

• short-rib thoracic dysplasia 10 with or without polydactyly

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Bardet-Biedl syndrome 20

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa 71

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short-rib thoracic dysplasia 9 with or without polydactyly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_015662.3.
• PP5: Variant 2-27476656-TAATATC-T is Pathogenic according to our data. Variant chr2-27476656-TAATATC-T is described in ClinVar as Pathogenic. ClinVar VariationId is 97030.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015662.3. 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
	IFT172	NM_015662.3	MANE Select	c.1390_1395delGATATT	p.Asp464_Ile465del	conservative_inframe_deletion	Exon 14 of 48	NP_056477.1
	IFT172	NM_001410739.1		c.1390_1395delGATATT	p.Asp464_Ile465del	conservative_inframe_deletion	Exon 14 of 48	NP_001397668.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT172	ENST00000260570.8	TSL:1 MANE Select	c.1390_1395delGATATT	p.Asp464_Ile465del	conservative_inframe_deletion	Exon 14 of 48	ENSP00000260570.3
	IFT172	ENST00000359466.10	TSL:1	c.1390_1395delGATATT	p.Asp464_Ile465del	conservative_inframe_deletion	Exon 14 of 15	ENSP00000352443.6
	IFT172	ENST00000675690.1		c.1390_1395delGATATT	p.Asp464_Ile465del	conservative_inframe_deletion	Exon 14 of 48	ENSP00000502283.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000419 AC: 6 AN: 1433614 Hom.: 0 AF XY: 0.00000419 AC XY: 3 AN XY: 715148

African (AFR) AF: 0.00 AC: 0 AN: 32878

American (AMR) AF: 0.00 AC: 0 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25944

East Asian (EAS) AF: 0.00 AC: 0 AN: 39560

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00000276 AC: 3 AN: 1086540

Other (OTH) AF: 0.0000168 AC: 1 AN: 59404

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Short-rib thoracic dysplasia 10 without polydactyly Pathogenic:1

Nov 07, 2013

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.2
Mutation Taster		=8/192	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs587777084; hg19: chr2-27699523; COSMIC: COSV105020540; COSMIC: COSV105020540;