rs2929282

Variant names:

• chr15-43953733-A-T
• rs2929282
• NM_032892.5:c.103-29424T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032892.5(FRMD5):​c.103-29424T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,170 control chromosomes in the GnomAD database, including 2,373 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 0.13 (2373 hom., cov: 32)
• Consequence: FRMD5 NM_032892.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 75 publications found

Genes affected

FRMD5 (HGNC:28214): (FERM domain containing 5) Enables integrin binding activity and protein kinase binding activity. Involved in negative regulation of cell motility; positive regulation of cell adhesion; and regulation of cell migration. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

FRMD5 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with eye movement abnormalities and ataxia

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD5	NM_032892.5	c.103-29424T>A		intron_variant	Intron 1 of 13	ENST00000417257.6	NP_116281.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD5	ENST00000417257.6	c.103-29424T>A		intron_variant	Intron 1 of 13	1	NM_032892.5	ENSP00000403067.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19428 AN: 152052 Hom.: 2369 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0773

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0588

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.128 AC: 19458 AN: 152170 Hom.: 2373 Cov.: 32 AF XY: 0.125 AC XY: 9338 AN XY: 74424

African (AFR) AF: 0.319 AC: 13235 AN: 41454

American (AMR) AF: 0.0774 AC: 1184 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3470

East Asian (EAS) AF: 0.0587 AC: 305 AN: 5192

South Asian (SAS) AF: 0.0683 AC: 329 AN: 4820

European-Finnish (FIN) AF: 0.0489 AC: 518 AN: 10600

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0471 AC: 3203 AN: 68008

Other (OTH) AF: 0.105 AC: 223 AN: 2114

Alfa AF: 0.0627 Hom.: 326

Bravo AF: 0.141

Asia WGS AF: 0.0890 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.55
PhyloP100		0.53
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: rs2929282; hg19: chr15-44245931;