Genetic Variant NM_001547.5:c.1056C>G (chr10-89307012-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001547.5(IFIT2):c.1056C>G(p.Asp352Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 30)

Failed GnomAD Quality Control

Consequence

IFIT2
NM_001547.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.871

Publications

55 publications found

Variant links:

Genes affected

IFIT2 (HGNC:5409): (interferon induced protein with tetratricopeptide repeats 2) Enables RNA binding activity. Involved in negative regulation of protein binding activity; positive regulation of apoptotic process; and response to virus. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

IFIT2 links:

LIPA (HGNC:6617): (lipase A, lysosomal acid type) This gene encodes lipase A, the lysosomal acid lipase (also known as cholesterol ester hydrolase). This enzyme functions in the lysosome to catalyze the hydrolysis of cholesteryl esters and triglycerides. Mutations in this gene can result in Wolman disease and cholesteryl ester storage disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014]

LIPA Gene-Disease associations (from GenCC):

lysosomal acid lipase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, ClinGen, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
cholesteryl ester storage disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Wolman disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LIPA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015794516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFIT2	NM_001547.5 link	c.1056C>G	p.Asp352Glu	missense_variant	Exon 2 of 2	ENST00000371826.4	NP_001538.4	P09913Q05DN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFIT2	ENST00000371826.4 link	c.1056C>G	p.Asp352Glu	missense_variant	Exon 2 of 2	1	NM_001547.5	ENSP00000360891.3		P09913

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152038

Hom.:

Cov.:

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

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74246

African (AFR)

AF:

0.00

AC:

AN:

41384

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2092

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.4

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.019

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.048

.;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.2

N;N;.

PhyloP100

0.87

PrimateAI

Benign

0.27

PROVEAN

Benign

1.9

.;N;.

REVEL

Benign

0.024

Sift

Benign

0.98

.;T;.

Sift4G

Benign

1.0

.;T;T

Polyphen

0.0

B;B;.

Vest4

0.016, 0.015

MutPred

0.32

Gain of disorder (P = 0.1214);Gain of disorder (P = 0.1214);Gain of disorder (P = 0.1214);

MVP

0.26

MPC

0.16

ClinPred

0.039

GERP RS

2.2

Varity_R

0.029

gMVP

0.072

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over