chr2-27445040-AG-A

Variant names:

• chr2-27445040-AG-A
• rs869025254
• NM_015662.3:c.5133delC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PVS1_Moderate PM2 BP6_Moderate

The NM_015662.3(IFT172):​c.5133delC​(p.Trp1712GlyfsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFT172 NM_015662.3 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.91
• 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]

KRTCAP3 (HGNC:28943): (keratinocyte associated protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0223 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 2-27445040-AG-A is Benign according to our data. Variant chr2-27445040-AG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 221929.Status of the report is criteria_provided_single_submitter, 1 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.5133delC	p.Trp1712GlyfsTer20	frameshift	Exon 47 of 48	NP_056477.1
	IFT172	NM_001410739.1		c.5067delC	p.Trp1690GlyfsTer20	frameshift	Exon 47 of 48	NP_001397668.1
	KRTCAP3	NM_001168364.2		c.*5+980delG		intron	N/A	NP_001161836.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT172	ENST00000260570.8	TSL:1 MANE Select	c.5133delC	p.Trp1712GlyfsTer20	frameshift	Exon 47 of 48	ENSP00000260570.3
	IFT172	ENST00000509128.5	TSL:1	n.*578delC		non_coding_transcript_exon	Exon 15 of 16	ENSP00000427255.1
	IFT172	ENST00000509128.5	TSL:1	n.*578delC		3_prime_UTR	Exon 15 of 16	ENSP00000427255.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anophthalmia-microphthalmia syndrome Benign:1

Jan 01, 2013

Paul Sabatier University EA-4555, Paul Sabatier University

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs869025254; hg19: chr2-27667907;