Genetic Variant FMNL2:c.360-10_360-9insA (chr2-152558730-T-TA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_052905.4(FMNL2):c.360-10_360-9insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,300 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

FMNL2
NM_052905.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMNL2	NM_052905.4 link	c.360-10_360-9insA		intron_variant	Intron 4 of 25	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.360-10_360-9insA		intron_variant	Intron 4 of 25	1	NM_052905.4	ENSP00000288670.9		Q96PY5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1412300

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702914

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:

32020

American (AMR)

AF:

0.00

AC:

AN:

41892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25616

East Asian (EAS)

AF:

0.00

AC:

AN:

39028

South Asian (SAS)

AF:

0.00

AC:

AN:

82920

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50784

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

9.29e-7

AC:

AN:

1075902

Other (OTH)

AF:

0.00

AC:

AN:

58494

⚠️ 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: 0.275

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

-1.6

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

Publications

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chr2-152558730-T-TA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over