1-240448048-G-T

Variant names:

• chr1-240448048-G-T
• rs10926263
• NM_020066.5:c.5060+9838G>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.5060+9838G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,014 control chromosomes in the GnomAD database, including 39,937 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 0.72 (39937 hom., cov: 32)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 3 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 (AMR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN2	NM_020066.5	c.5060+9838G>T		intron_variant	Intron 16 of 17	ENST00000319653.14	NP_064450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000319653.14	c.5060+9838G>T		intron_variant	Intron 16 of 17	5	NM_020066.5	ENSP00000318884.9

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109829 AN: 151896 Hom.: 39918 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.723 AC: 109899 AN: 152014 Hom.: 39937 Cov.: 32 AF XY: 0.722 AC XY: 53624 AN XY: 74284

African (AFR) AF: 0.680 AC: 28171 AN: 41444

American (AMR) AF: 0.807 AC: 12328 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2823 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3125 AN: 5138

South Asian (SAS) AF: 0.617 AC: 2971 AN: 4814

European-Finnish (FIN) AF: 0.685 AC: 7236 AN: 10562

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50705 AN: 67994

Other (OTH) AF: 0.748 AC: 1577 AN: 2108

Alfa AF: 0.742 Hom.: 47281

Bravo AF: 0.733

Asia WGS AF: 0.617 AC: 2147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.75
PhyloP100		0.012
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: rs10926263; hg19: chr1-240611348;