rs9688110

Positions:

• chr5-151584241-G-A
• chr5-151584241-G-C

Variant summary

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

The NM_001447.3(FAT2):​c.-21+6924C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,444 control chromosomes in the GnomAD database, including 8,314 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 0.33 (8314 hom., cov: 29)
• Consequence: FAT2 NM_001447.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.724

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]

FAT2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAT2	NM_001447.3	c.-21+6924C>T		intron_variant		ENST00000261800.6	NP_001438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAT2	ENST00000261800.6	c.-21+6924C>T		intron_variant		1	NM_001447.3	ENSP00000261800.5

Frequencies

GnomAD3 genomes AF: 0.330 AC: 49998 AN: 151326 Hom.: 8307 Cov.: 29

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.330 AC: 50024 AN: 151444 Hom.: 8314 Cov.: 29 AF XY: 0.330 AC XY: 24387 AN XY: 73958

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.326

Alfa AF: 0.316 Hom.: 12882

Bravo AF: 0.324

Asia WGS AF: 0.371 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.17
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9688110; hg19: chr5-150963802; COSMIC: COSV60211921;