chr1-240207698-A-C

Variant names:

• chr1-240207698-A-C
• rs199866405
• NM_020066.5:c.2886A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001305424.2(FMN2):​c.2898A>C​(p.Ala966Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A966A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FMN2 NM_001305424.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-2.99 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305424.2. 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.2886A>C	p.Ala962Ala	synonymous	Exon 5 of 18	NP_064450.3
	FMN2	NM_001305424.2		c.2898A>C	p.Ala966Ala	synonymous	Exon 6 of 19	NP_001292353.1
	FMN2	NM_001348094.2		c.1986+19436A>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.2886A>C	p.Ala962Ala	synonymous	Exon 5 of 18	ENSP00000318884.9
	FMN2	ENST00000679980.1		c.188+706A>C		intron	N/A	ENSP00000505449.1
	FMN2	ENST00000681210.1		c.285+19436A>C		intron	N/A	ENSP00000505131.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 49100 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 715418 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 358464

African (AFR) AF: 0.00 AC: 0 AN: 14604

American (AMR) AF: 0.00 AC: 0 AN: 29028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12024

East Asian (EAS) AF: 0.00 AC: 0 AN: 15966

South Asian (SAS) AF: 0.00 AC: 0 AN: 47052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1870

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 536488

Other (OTH) AF: 0.00 AC: 0 AN: 27994

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 49100 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 23096

African (AFR) AF: 0.00 AC: 0 AN: 10952

American (AMR) AF: 0.00 AC: 0 AN: 4136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1274

East Asian (EAS) AF: 0.00 AC: 0 AN: 1556

South Asian (SAS) AF: 0.00 AC: 0 AN: 1384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 68

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 26140

Other (OTH) AF: 0.00 AC: 0 AN: 652

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.35
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism

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: rs199866405; hg19: chr1-240370998;