chr2-27481061-A-G

Position:

• chr2-27481061-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_015662.3(IFT172):​c.770T>C​(p.Leu257Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: IFT172 NM_015662.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.58

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.873
• PP5: Variant 2-27481061-A-G is Pathogenic according to our data. Variant chr2-27481061-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 191369.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-27481061-A-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT172	NM_015662.3	c.770T>C	p.Leu257Pro	missense_variant	8/48	ENST00000260570.8	NP_056477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT172	ENST00000260570.8	c.770T>C	p.Leu257Pro	missense_variant	8/48	1	NM_015662.3	ENSP00000260570.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinitis pigmentosa 71 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D;.;T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.3	M;M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.96	D;.;.
Vest4		0.97
MutPred		0.59		Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);.;
MVP		0.70
MPC		0.81
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.88
gMVP		0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs786205857; hg19: chr2-27703928;