Genetic Variant FMNL2:p.Pro564SerfsTer21 (chr2-152619554-C-CACCCCCCCCCCCA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_052905.4(FMNL2):c.1673_1674insACCCCCCCCCCCA(p.Pro564SerfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,352 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

FMNL2
NM_052905.4 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -9.94

Publications

0 publications found

Variant links:

Genes affected

FMNL2 (HGNC:18267): (formin like 2) This gene encodes a formin-related protein. Formin-related proteins have been implicated in morphogenesis, cytokinesis, and cell polarity. Alternatively spliced transcript variants encoding different isoforms have been described but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

FMNL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMNL2	NM_052905.4 link	c.1673_1674insACCCCCCCCCCCA	p.Pro564SerfsTer21	frameshift_variant	Exon 15 of 26	ENST00000288670.14	NP_443137.2	Q96PY5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMNL2	ENST00000288670.14 link	c.1673_1674insACCCCCCCCCCCA	p.Pro564SerfsTer21	frameshift_variant	Exon 15 of 26	1	NM_052905.4	ENSP00000288670.9		Q96PY5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.22e-7

AC:

AN:

1385352

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

683424

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31322

American (AMR)

AF:

0.00

AC:

AN:

35458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24980

East Asian (EAS)

AF:

0.00

AC:

AN:

35592

South Asian (SAS)

AF:

0.0000128

AC:

AN:

78350

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48502

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4180

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1069586

Other (OTH)

AF:

0.00

AC:

AN:

57382

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-9.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over