rs9287234

Variant names:

• chr1-240403073-G-A
• rs9287234
• NM_020066.5:c.4910+10511G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-240403073-G-A
• chr1-240403073-G-C
• chr1-240403073-G-T

Variant summary

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

The NM_020066.5(FMN2):​c.4910+10511G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,182 control chromosomes in the GnomAD database, including 52,207 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 0.83 (52207 hom., cov: 33)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020066.5. 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
	FMN2	NM_020066.5	MANE Select	c.4910+10511G>A		intron	N/A	NP_064450.3
	FMN2	NM_001305424.2		c.4922+10511G>A		intron	N/A	NP_001292353.1
	FMN2	NM_001348094.2		c.2738+10511G>A		intron	N/A	NP_001335023.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN2	ENST00000319653.14	TSL:5 MANE Select	c.4910+10511G>A		intron	N/A	ENSP00000318884.9
	FMN2	ENST00000679980.1		c.1178+10511G>A		intron	N/A	ENSP00000505449.1
	FMN2	ENST00000681210.1		c.1130+10511G>A		intron	N/A	ENSP00000505131.1

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125858 AN: 152060 Hom.: 52155 Cov.: 33

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.866

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.828 AC: 125974 AN: 152182 Hom.: 52207 Cov.: 33 AF XY: 0.824 AC XY: 61269 AN XY: 74378

African (AFR) AF: 0.824 AC: 34195 AN: 41524

American (AMR) AF: 0.793 AC: 12113 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 3035 AN: 3472

East Asian (EAS) AF: 0.812 AC: 4194 AN: 5166

South Asian (SAS) AF: 0.839 AC: 4049 AN: 4824

European-Finnish (FIN) AF: 0.797 AC: 8438 AN: 10584

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57139 AN: 68008

Other (OTH) AF: 0.846 AC: 1788 AN: 2114

Alfa AF: 0.833 Hom.: 6561

Bravo AF: 0.829

Asia WGS AF: 0.850 AC: 2950 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.12
DANN	Benign	0.26
PhyloP100		-0.79
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: rs9287234; hg19: chr1-240566373; COSMIC: COSV60423738; COSMIC: COSV60423738;