rs16840114

Variant names:

• chr1-240462131-A-G
• rs16840114
• NM_020066.5:c.5061-10241A>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.5061-10241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0659 in 152,094 control chromosomes in the GnomAD database, including 418 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 0.066 (418 hom., cov: 32)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 7 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.118 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN2	NM_020066.5	MANE Select	c.5061-10241A>G		intron	N/A	NP_064450.3
	FMN2	NM_001305424.2		c.5073-10241A>G		intron	N/A	NP_001292353.1
	FMN2	NM_001348094.2		c.2889-10241A>G		intron	N/A	NP_001335023.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN2	ENST00000319653.14	TSL:5 MANE Select	c.5061-10241A>G		intron	N/A	ENSP00000318884.9	Q9NZ56-1
	FMN2	ENST00000543681.2	TSL:1	n.1951+2688A>G		intron	N/A
	FMN2	ENST00000679980.1		c.1329-10241A>G		intron	N/A	ENSP00000505449.1	A0A7P0T994

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10028 AN: 151976 Hom.: 420 Cov.: 32

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.0975

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0622

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.0659 AC: 10026 AN: 152094 Hom.: 418 Cov.: 32 AF XY: 0.0715 AC XY: 5313 AN XY: 74352

African (AFR) AF: 0.0367 AC: 1524 AN: 41494

American (AMR) AF: 0.0795 AC: 1215 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0982 AC: 341 AN: 3472

East Asian (EAS) AF: 0.0979 AC: 506 AN: 5170

South Asian (SAS) AF: 0.127 AC: 611 AN: 4820

European-Finnish (FIN) AF: 0.129 AC: 1362 AN: 10560

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0622 AC: 4227 AN: 67982

Other (OTH) AF: 0.0762 AC: 161 AN: 2112

Alfa AF: 0.0649 Hom.: 124

Bravo AF: 0.0626

Asia WGS AF: 0.0930 AC: 325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.61
DANN	Benign	0.60
PhyloP100		0.11
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: rs16840114; hg19: chr1-240625431;