rs1982530

Variant names:

• chr1-240135517-T-C
• rs1982530
• NM_020066.5:c.1782+12172T>C

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+12172T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 152,220 control chromosomes in the GnomAD database, including 662 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 0.088 (662 hom., cov: 32)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 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.1782+12172T>C		intron	N/A	NP_064450.3
	FMN2	NM_001305424.2		c.1782+12172T>C		intron	N/A	NP_001292353.1
	FMN2	NM_001348094.2		c.1782+12172T>C		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.1782+12172T>C		intron	N/A	ENSP00000318884.9
	FMN2	ENST00000681210.1		c.81+12172T>C		intron	N/A	ENSP00000505131.1
	FMN2	ENST00000681824.1		c.81+12172T>C		intron	N/A	ENSP00000505818.1

Frequencies

GnomAD3 genomes AF: 0.0879 AC: 13369 AN: 152102 Hom.: 660 Cov.: 32

Gnomad AFR AF: 0.0692

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0946

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0750

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0827

Gnomad OTH AF: 0.0982

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

GnomAD4 genome AF: 0.0879 AC: 13383 AN: 152220 Hom.: 662 Cov.: 32 AF XY: 0.0893 AC XY: 6645 AN XY: 74436

African (AFR) AF: 0.0693 AC: 2878 AN: 41528

American (AMR) AF: 0.141 AC: 2157 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0946 AC: 328 AN: 3468

East Asian (EAS) AF: 0.115 AC: 598 AN: 5182

South Asian (SAS) AF: 0.155 AC: 750 AN: 4828

European-Finnish (FIN) AF: 0.0750 AC: 795 AN: 10598

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0828 AC: 5629 AN: 68020

Other (OTH) AF: 0.0962 AC: 203 AN: 2110

Alfa AF: 0.0879 Hom.: 1004

Bravo AF: 0.0925

Asia WGS AF: 0.111 AC: 386 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.23
PhyloP100		-0.57
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: rs1982530; hg19: chr1-240298817;