rs3097779

Positions:

• chr5-151560146-A-C
• chr5-151560146-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001447.3(FAT2):​c.3574+3179T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 152,016 control chromosomes in the GnomAD database, including 32,535 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32535 hom., cov: 32)
• Consequence: FAT2 NM_001447.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAT2	NM_001447.3	c.3574+3179T>G		intron_variant		ENST00000261800.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAT2	ENST00000261800.6	c.3574+3179T>G		intron_variant		1	NM_001447.3	P1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99126 AN: 151900 Hom.: 32491 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.663

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.653 AC: 99223 AN: 152016 Hom.: 32535 Cov.: 32 AF XY: 0.651 AC XY: 48419 AN XY: 74348

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.720

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.662

Alfa AF: 0.673 Hom.: 15769

Bravo AF: 0.663

Asia WGS AF: 0.628 AC: 2181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.1
DANN	Benign	0.64

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: rs3097779; hg19: chr5-150939707;