12-2818151-G-A

Variant names:

• chr12-2818151-G-A
• rs368815825
• NM_018463.4:c.280G>A

Variant summary

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

The NM_018463.4(ITFG2):​c.280G>A​(p.Asp94Asn) 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. 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. D94Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITFG2 NM_018463.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.73
• 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, 0.8

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.280G>A	p.Asp94Asn	missense	Exon 4 of 12	NP_060933.3
	ITFG2	NR_130744.3		n.373G>A		non_coding_transcript_exon	Exon 4 of 14
	ITFG2	NR_147202.2		n.373G>A		non_coding_transcript_exon	Exon 4 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITFG2	ENST00000228799.7	TSL:1 MANE Select	c.280G>A	p.Asp94Asn	missense	Exon 4 of 12	ENSP00000228799.2	Q969R8-1
	ITFG2	ENST00000537851.5	TSL:1	n.97-1935G>A		intron	N/A	ENSP00000445769.1	F5H1D0
	ITFG2	ENST00000917242.1		c.280G>A	p.Asp94Asn	missense	Exon 4 of 12	ENSP00000587301.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.7
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.74	N
REVEL	Uncertain	0.38
Sift	Benign	0.20	T
Sift4G	Benign	0.46	T
Polyphen		1.0	D
Vest4		0.74
MutPred		0.45		Gain of catalytic residue at W89 (P = 0)
MVP		0.88
MPC		0.99
ClinPred		0.90	D
GERP RS		4.7
Varity_R		0.14
gMVP		0.67
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs368815825; hg19: chr12-2927317;