rs720163

Variant names:

• chr1-240132575-A-G
• rs720163
• NM_020066.5:c.1782+9230A>G

Variant summary

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

The NM_020066.5(FMN2):​c.1782+9230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,000 control chromosomes in the GnomAD database, including 6,988 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 0.28 (6988 hom., cov: 32)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 4 publications found

Genes affected

FMN2 (HGNC:14074): (formin 2) This gene is a member of the formin homology protein family. The encoded protein is thought to have essential roles in organization of the actin cytoskeleton and in cell polarity. This protein mediates the formation of an actin mesh that positions the spindle during oogenesis and also regulates the formation of actin filaments in the nucleus. This protein also forms a perinuclear actin/focal-adhesion system that regulates the shape and position of the nucleus during cell migration. Mutations in this gene have been associated with infertility and also with an autosomal recessive form of intellectual disability (MRT47). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2017]

FMN2 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 47

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN2	NM_020066.5	c.1782+9230A>G		intron_variant	Intron 2 of 17	ENST00000319653.14	NP_064450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000319653.14	c.1782+9230A>G		intron_variant	Intron 2 of 17	5	NM_020066.5	ENSP00000318884.9

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42967 AN: 151882 Hom.: 6988 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.283 AC: 42983 AN: 152000 Hom.: 6988 Cov.: 32 AF XY: 0.281 AC XY: 20875 AN XY: 74298

African (AFR) AF: 0.113 AC: 4684 AN: 41478

American (AMR) AF: 0.279 AC: 4264 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1487 AN: 3470

East Asian (EAS) AF: 0.226 AC: 1159 AN: 5136

South Asian (SAS) AF: 0.282 AC: 1357 AN: 4820

European-Finnish (FIN) AF: 0.340 AC: 3596 AN: 10568

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25311 AN: 67948

Other (OTH) AF: 0.316 AC: 667 AN: 2110

Alfa AF: 0.314 Hom.: 1281

Bravo AF: 0.273

Asia WGS AF: 0.257 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.2
DANN	Benign	0.64
PhyloP100		1.0
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: rs720163; hg19: chr1-240295875;