Genetic Variant ITFG2:p.Arg141Pro (chr12-2820101-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018463.4(ITFG2):c.422G>C(p.Arg141Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R141H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ITFG2
NM_018463.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.00

Publications

0 publications found

Variant links:

Genes affected

ITFG2 (HGNC:30879): (integrin alpha FG-GAP repeat containing 2) Involved in cellular response to amino acid starvation; cellular response to glucose starvation; and negative regulation of TORC1 signaling. Located in lysosomal membrane. Part of KICSTOR complex. [provided by Alliance of Genome Resources, Apr 2022]

ITFG2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1428205).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018463.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ITFG2	NM_018463.4	MANE Select	c.422G>C	p.Arg141Pro	missense	Exon 5 of 12	NP_060933.3
ITFG2	NR_130744.3		n.591G>C		non_coding_transcript_exon	Exon 5 of 14
ITFG2	NR_147202.2		n.493G>C		non_coding_transcript_exon	Exon 5 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITFG2	ENST00000228799.7	TSL:1 MANE Select	c.422G>C	p.Arg141Pro	missense	Exon 5 of 12	ENSP00000228799.2	Q969R8-1
ITFG2	ENST00000537851.5	TSL:1	n.112G>C		non_coding_transcript_exon	Exon 2 of 9	ENSP00000445769.1	F5H1D0
ITFG2	ENST00000917242.1		c.422G>C	p.Arg141Pro	missense	Exon 5 of 12	ENSP00000587301.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725728

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25860

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53312

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110686

Other (OTH)

AF:

0.00

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.048

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.020

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

4.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.92

REVEL

Benign

0.092

Sift

Benign

0.20

Sift4G

Benign

0.20

Polyphen

0.23

Vest4

0.36

MutPred

0.41

Gain of catalytic residue at E142 (P = 0)

MVP

0.71

MPC

0.50

ClinPred

0.51

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.32

gMVP

0.71

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over