rs1432862

Variant names:

• chr5-151567212-G-A
• rs1432862
• NM_001447.3:c.1720C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-151567212-G-A
• chr5-151567212-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001447.3(FAT2):​c.1720C>T​(p.Arg574Cys) variant causes a missense change. The variant allele was found at a frequency of 0.503 in 1,613,572 control chromosomes in the GnomAD database, including 207,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R574H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.48 (18000 hom., cov: 32)
  • Exomes 𝑓: 0.51 (189845 hom.)
• Consequence: FAT2 NM_001447.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 6.76
• Publications: 27 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia 45

  Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021697283).
• BP6: Variant 5-151567212-G-A is Benign according to our data. Variant chr5-151567212-G-A is described in ClinVar as Benign. ClinVar VariationId is 1249058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT2	NM_001447.3	c.1720C>T	p.Arg574Cys	missense_variant	Exon 2 of 24	ENST00000261800.6	NP_001438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT2	ENST00000261800.6	c.1720C>T	p.Arg574Cys	missense_variant	Exon 2 of 24	1	NM_001447.3	ENSP00000261800.5

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73489 AN: 151866 Hom.: 17987 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.487

GnomAD2 exomes AF: 0.466 AC: 116880 AN: 251070 AF XY: 0.468

Gnomad AFR exome AF: 0.434

Gnomad AMR exome AF: 0.340

Gnomad ASJ exome AF: 0.529

Gnomad EAS exome AF: 0.359

Gnomad FIN exome AF: 0.550

Gnomad NFE exome AF: 0.531

Gnomad OTH exome AF: 0.507

GnomAD4 exome AF: 0.505 AC: 738745 AN: 1461588 Hom.: 189845 Cov.: 60 AF XY: 0.502 AC XY: 364928 AN XY: 727088

African (AFR) AF: 0.435 AC: 14568 AN: 33474

American (AMR) AF: 0.352 AC: 15729 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 13982 AN: 26126

East Asian (EAS) AF: 0.324 AC: 12851 AN: 39700

South Asian (SAS) AF: 0.362 AC: 31248 AN: 86216

European-Finnish (FIN) AF: 0.546 AC: 29152 AN: 53394

Middle Eastern (MID) AF: 0.463 AC: 2672 AN: 5768

European-Non Finnish (NFE) AF: 0.529 AC: 587985 AN: 1111824

Other (OTH) AF: 0.506 AC: 30558 AN: 60382

GnomAD4 genome AF: 0.484 AC: 73527 AN: 151984 Hom.: 18000 Cov.: 32 AF XY: 0.481 AC XY: 35715 AN XY: 74286

African (AFR) AF: 0.438 AC: 18168 AN: 41436

American (AMR) AF: 0.445 AC: 6799 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1843 AN: 3468

East Asian (EAS) AF: 0.348 AC: 1799 AN: 5174

South Asian (SAS) AF: 0.362 AC: 1742 AN: 4816

European-Finnish (FIN) AF: 0.553 AC: 5828 AN: 10548

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35860 AN: 67964

Other (OTH) AF: 0.483 AC: 1020 AN: 2112

Alfa AF: 0.509 Hom.: 68324

Bravo AF: 0.475

TwinsUK AF: 0.518 AC: 1922

ALSPAC AF: 0.531 AC: 2045

ESP6500AA AF: 0.439 AC: 1936

ESP6500EA AF: 0.523 AC: 4501

ExAC AF: 0.467 AC: 56713

Asia WGS AF: 0.384 AC: 1335 AN: 3478

EpiCase AF: 0.526

EpiControl AF: 0.531

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

FAT2-related disorder Benign:1

Jul 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Spinocerebellar ataxia 45 Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.8
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.28
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.094
MPC		0.52
ClinPred		0.033	T
GERP RS		4.3
Varity_R		0.33
gMVP		0.53
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1432862; hg19: chr5-150946773; COSMIC: COSV55815795;