Genetic Variant FMNL2:c.360-10_360-9insTC (chr2-152558730-T-TTC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_052905.4(FMNL2):c.360-10_360-9insTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,558,688 control chromosomes in the GnomAD database, including 24 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0089 ( 19 hom., cov: 21)

Exomes 𝑓: 0.0030 ( 5 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: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00894 (1348/150802) while in subpopulation AFR AF = 0.0299 (1224/40914). AF 95% confidence interval is 0.0285. There are 19 homozygotes in GnomAd4. There are 669 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.00888

AC:

1338

AN:

150692

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0298

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00567

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000292

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.000280

Gnomad OTH

AF:

0.00635

GnomAD2 exomes

AF:

0.00343

AC:

731

AN:

213212

AF XY:

0.00300

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.00353

Gnomad ASJ exome

AF:

0.000875

Gnomad EAS exome

AF:

0.00294

Gnomad FIN exome

AF:

0.00205

Gnomad NFE exome

AF:

0.00200

Gnomad OTH exome

AF:

0.00367

GnomAD4 exome

AF:

0.00297

AC:

4176

AN:

1407886

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

1930

AN XY:

700760

show subpopulations

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

African (AFR)

AF:

0.0327

AC:

1035

AN:

31666

American (AMR)

AF:

0.00357

AC:

149

AN:

41776

Ashkenazi Jewish (ASJ)

AF:

0.000899

AC:

AN:

25592

East Asian (EAS)

AF:

0.00211

AC:

AN:

38888

South Asian (SAS)

AF:

0.00163

AC:

135

AN:

82718

European-Finnish (FIN)

AF:

0.00156

AC:

AN:

50642

Middle Eastern (MID)

AF:

0.00391

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.00227

AC:

2439

AN:

1072692

Other (OTH)

AF:

0.00364

AC:

212

AN:

58290

⚠️ 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: 0.303

Heterozygous variant carriers

305

611

916

1222

1527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00894

AC:

1348

AN:

150802

Hom.:

Cov.:

AF XY:

0.00910

AC XY:

669

AN XY:

73556

show subpopulations

African (AFR)

AF:

0.0299

AC:

1224

AN:

40914

American (AMR)

AF:

0.00573

AC:

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4754

European-Finnish (FIN)

AF:

0.000292

AC:

AN:

10262

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000280

AC:

AN:

67804

Other (OTH)

AF:

0.00678

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

117

175

234

292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00316

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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chr2-152558730-T-TTC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over