1-240123416-G-T

Variant names:

• chr1-240123416-G-T
• rs3738433
• NM_020066.5:c.1782+71G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020066.5(FMN2):​c.1782+71G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,325,688 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.1782+71G>T		intron	N/A	NP_064450.3
	FMN2	NM_001305424.2		c.1782+71G>T		intron	N/A	NP_001292353.1
	FMN2	NM_001348094.2		c.1782+71G>T		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.1782+71G>T		intron	N/A	ENSP00000318884.9	Q9NZ56-1
	FMN2	ENST00000681210.1		c.81+71G>T		intron	N/A	ENSP00000505131.1	A0A7P0Z432
	FMN2	ENST00000681824.1		c.81+71G>T		intron	N/A	ENSP00000505818.1	A0A7P0TA49

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000158 AC: 21 AN: 1325688 Hom.: 0 AF XY: 0.0000214 AC XY: 14 AN XY: 655350

African (AFR) AF: 0.00 AC: 0 AN: 29450

American (AMR) AF: 0.00 AC: 0 AN: 33554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20932

East Asian (EAS) AF: 0.0000266 AC: 1 AN: 37660

South Asian (SAS) AF: 0.00 AC: 0 AN: 71814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5258

European-Non Finnish (NFE) AF: 0.0000194 AC: 20 AN: 1030386

Other (OTH) AF: 0.00 AC: 0 AN: 54946

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.71
PhyloP100		0.32
PromoterAI		-0.12	Neutral

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: rs3738433; hg19: chr1-240286716;