5-151567212-G-C

Position:

• chr5-151567212-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001447.3(FAT2):​c.1720C>G​(p.Arg574Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. R574C) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: FAT2 NM_001447.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.76

Genes affected

FAT2 (HGNC:3596): (FAT atypical cadherin 2) This gene is the second identified human homolog of the Drosophila fat gene, which encodes a tumor suppressor essential for controlling cell proliferation during Drosophila development. The gene product is a member of the cadherin superfamily, a group of integral membrane proteins characterized by the presence of cadherin-type repeats. In addition to containing 34 tandem cadherin-type repeats, the gene product has two epidermal growth factor (EGF)-like repeats and one laminin G domain. This protein most likely functions as a cell adhesion molecule, controlling cell proliferation and playing an important role in cerebellum development. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, FAT2
• BP4: Computational evidence support a benign effect (MetaRNN=0.22470051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAT2	NM_001447.3	c.1720C>G	p.Arg574Gly	missense_variant	2/24	ENST00000261800.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAT2	ENST00000261800.6	c.1720C>G	p.Arg574Gly	missense_variant	2/24	1	NM_001447.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151950 Hom.: 0 Cov.: 32 FAILED QC

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.: 60

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151950 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74192

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	0.72	P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.14
Sift	Benign	0.15	T
Sift4G	Benign	0.063	T
Polyphen		0.18	B
Vest4		0.095
MutPred		0.51		Loss of catalytic residue at R574 (P = 0.1187);
MVP		0.73
MPC		0.16
ClinPred		0.59	D
GERP RS		4.3
Varity_R		0.20
gMVP		0.51

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: rs1432862; hg19: chr5-150946773;