NM_018463.4:c.201C>G

Variant names:

• chr12-2817917-C-G
• NM_018463.4:c.201C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018463.4(ITFG2):​c.201C>G​(p.Cys67Trp) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITFG2 NM_018463.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.36
• Publications: 0 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.807

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITFG2	NM_018463.4	MANE Select	c.201C>G	p.Cys67Trp	missense	Exon 3 of 12	NP_060933.3
	ITFG2	NR_130744.3		n.294C>G		non_coding_transcript_exon	Exon 3 of 14
	ITFG2	NR_147202.2		n.294C>G		non_coding_transcript_exon	Exon 3 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITFG2	ENST00000228799.7	TSL:1 MANE Select	c.201C>G	p.Cys67Trp	missense	Exon 3 of 12	ENSP00000228799.2	Q969R8-1
	ITFG2	ENST00000537851.5	TSL:1	n.97-2169C>G		intron	N/A	ENSP00000445769.1	F5H1D0
	ITFG2	ENST00000917242.1		c.201C>G	p.Cys67Trp	missense	Exon 3 of 12	ENSP00000587301.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.085	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		-2.4
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.62		Gain of catalytic residue at L65 (P = 0)
MVP		0.29
MPC		1.2
ClinPred		1.0	D
GERP RS		-9.6
Varity_R		0.84
gMVP		0.88
Mutation Taster		=17/83	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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

hg19: chr12-2927083;