rs2288777

Positions:

• chr5-151540547-A-G
• chr5-151540547-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001447.3(FAT2):​c.9039+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 1,590,006 control chromosomes in the GnomAD database, including 5,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (878 hom., cov: 32)
  • Exomes 𝑓: 0.075 (4358 hom.)
• Consequence: FAT2 NM_001447.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.44

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]

SLC36A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-151540547-A-G is Benign according to our data. Variant chr5-151540547-A-G is described in ClinVar as [Benign]. Clinvar id is 1281368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAT2	NM_001447.3	c.9039+20T>C		intron_variant		ENST00000261800.6	NP_001438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAT2	ENST00000261800.6	c.9039+20T>C		intron_variant		1	NM_001447.3	ENSP00000261800	P1

Frequencies

GnomAD3 genomes AF: 0.0983 AC: 14734 AN: 149836 Hom.: 864 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0727

Gnomad FIN AF: 0.0451

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.0918

GnomAD3 exomes AF: 0.0819 AC: 19825 AN: 242070 Hom.: 878 AF XY: 0.0796 AC XY: 10394 AN XY: 130592

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.0725

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.134

Gnomad SAS exome AF: 0.0725

Gnomad FIN exome AF: 0.0465

Gnomad NFE exome AF: 0.0706

Gnomad OTH exome AF: 0.0809

GnomAD4 exome AF: 0.0745 AC: 107286 AN: 1440058 Hom.: 4358 Cov.: 31 AF XY: 0.0740 AC XY: 52803 AN XY: 713506

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.0709

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.0739

Gnomad4 FIN exome AF: 0.0469

Gnomad4 NFE exome AF: 0.0694

Gnomad4 OTH exome AF: 0.0803

GnomAD4 genome AF: 0.0987 AC: 14793 AN: 149948 Hom.: 878 Cov.: 32 AF XY: 0.0968 AC XY: 7069 AN XY: 73038

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0749

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.0733

Gnomad4 FIN AF: 0.0451

Gnomad4 NFE AF: 0.0700

Gnomad4 OTH AF: 0.0985

Alfa AF: 0.0759 Hom.: 275

Bravo AF: 0.104

Asia WGS AF: 0.148 AC: 512 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.020
DANN	Benign	0.60

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: rs2288777; hg19: chr5-150920108;