rs9688110

Variant names:

• chr5-151584241-G-A
• rs9688110
• NM_001447.3:c.-21+6924C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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 rank	MANE	Protein	UniProt
FAT2	NM_001447.3	c.-21+6924C>T		intron_variant	Intron 1 of 23	ENST00000261800.6	NP_001438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT2	ENST00000261800.6	c.-21+6924C>T		intron_variant	Intron 1 of 23	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

African (AFR) AF: 0.345 AC: 14240 AN: 41264

American (AMR) AF: 0.298 AC: 4522 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 986 AN: 3470

East Asian (EAS) AF: 0.333 AC: 1703 AN: 5110

South Asian (SAS) AF: 0.472 AC: 2259 AN: 4784

European-Finnish (FIN) AF: 0.288 AC: 3008 AN: 10450

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22141 AN: 67878

Other (OTH) AF: 0.326 AC: 681 AN: 2092

Alfa AF: 0.322 Hom.: 31984

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
PhyloP100		-0.72

Splicing

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

Other links and lift over

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