rs11810574

Variant names:

• chr1-240120436-A-G
• rs11810574
• NM_020066.5:c.1616-2743A>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.1616-2743A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0685 in 152,290 control chromosomes in the GnomAD database, including 451 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 0.068 (451 hom., cov: 33)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742
• Publications: 6 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN2	NM_020066.5	c.1616-2743A>G		intron_variant	Intron 1 of 17	ENST00000319653.14	NP_064450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000319653.14	c.1616-2743A>G		intron_variant	Intron 1 of 17	5	NM_020066.5	ENSP00000318884.9
FMN2	ENST00000447095.5	c.-86-2743A>G		intron_variant	Intron 2 of 6	3		ENSP00000409308.1

Frequencies

GnomAD3 genomes AF: 0.0684 AC: 10410 AN: 152172 Hom.: 449 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0364

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.0535

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

GnomAD4 genome AF: 0.0685 AC: 10426 AN: 152290 Hom.: 451 Cov.: 33 AF XY: 0.0652 AC XY: 4857 AN XY: 74464

African (AFR) AF: 0.114 AC: 4732 AN: 41560

American (AMR) AF: 0.0381 AC: 583 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.0373 AC: 180 AN: 4828

European-Finnish (FIN) AF: 0.0408 AC: 433 AN: 10614

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0626 AC: 4257 AN: 68028

Other (OTH) AF: 0.0568 AC: 120 AN: 2114

Alfa AF: 0.0636 Hom.: 1106

Bravo AF: 0.0700

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.3
DANN	Benign	0.52
PhyloP100		0.74
Mutation Taster		=98/2	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: rs11810574; hg19: chr1-240283736;