5-151540547-A-G

Variant names:

• chr5-151540547-A-G
• rs2288777
• NM_001447.3:c.9039+20T>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.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
• Publications: 5 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]

SLC36A1 (HGNC:18761): (solute carrier family 36 member 1) This gene encodes a member of the eukaryote-specific amino acid/auxin permease (AAAP) 1 transporter family. The encoded protein functions as a proton-dependent, small amino acid transporter. This gene is clustered with related family members on chromosome 5q33.1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001447.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAT2	NM_001447.3	MANE Select	c.9039+20T>C		intron	N/A	NP_001438.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAT2	ENST00000261800.6	TSL:1 MANE Select	c.9039+20T>C		intron	N/A	ENSP00000261800.5

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

GnomAD2 exomes AF: 0.0819 AC: 19825 AN: 242070 AF XY: 0.0796

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 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

African (AFR) AF: 0.161 AC: 5229 AN: 32548

American (AMR) AF: 0.0709 AC: 3118 AN: 44000

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 3099 AN: 25400

East Asian (EAS) AF: 0.142 AC: 5576 AN: 39282

South Asian (SAS) AF: 0.0739 AC: 6185 AN: 83666

European-Finnish (FIN) AF: 0.0469 AC: 2482 AN: 52890

Middle Eastern (MID) AF: 0.122 AC: 624 AN: 5104

European-Non Finnish (NFE) AF: 0.0694 AC: 76214 AN: 1097938

Other (OTH) AF: 0.0803 AC: 4759 AN: 59230

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

African (AFR) AF: 0.163 AC: 6613 AN: 40646

American (AMR) AF: 0.0749 AC: 1125 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 411 AN: 3462

East Asian (EAS) AF: 0.144 AC: 735 AN: 5106

South Asian (SAS) AF: 0.0733 AC: 342 AN: 4668

European-Finnish (FIN) AF: 0.0451 AC: 458 AN: 10164

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0700 AC: 4730 AN: 67578

Other (OTH) AF: 0.0985 AC: 206 AN: 2092

Alfa AF: 0.0770 Hom.: 314

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

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.020
DANN	Benign	0.60
PhyloP100		-2.4
Mutation Taster		=100/0	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: rs2288777; hg19: chr5-150920108; COSMIC: COSV107240157;