dbSNP rs17453240: CFL2:c.*2903C>G (chr14-34709962-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138638.5(CFL2):c.*2903C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 152,212 control chromosomes in the GnomAD database, including 494 homozygotes. 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: 𝑓 0.076 ( 493 hom., cov: 32)

Exomes 𝑓: 0.064 ( 1 hom. )

Consequence

CFL2
NM_138638.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.608

Publications

2 publications found

Variant links:

Genes affected

CFL2 (HGNC:1875): (cofilin 2) This gene encodes an intracellular protein that is involved in the regulation of actin-filament dynamics. This protein is a major component of intranuclear and cytoplasmic actin rods. It can bind G- and F-actin in a 1:1 ratio of cofilin to actin, and it reversibly controls actin polymerization and depolymerization in a pH-dependent manner. Mutations in this gene cause nemaline myopathy type 7, a form of congenital myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

CFL2 Gene-Disease associations (from GenCC):

nemaline myopathy 7
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen
typical nemaline myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CFL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFL2	NM_138638.5 link	c.*2903C>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000298159.11	NP_619579.1	Q9Y281-1Q549N0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFL2	ENST00000298159.11 link	c.*2903C>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_138638.5	ENSP00000298159.6		Q9Y281-1

Frequencies

GnomAD3 genomes

AF:

0.0759

AC:

11540

AN:

152016

Hom.:

493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0423

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0782

Gnomad ASJ

AF:

0.0686

Gnomad EAS

AF:

0.0853

Gnomad SAS

AF:

0.0496

Gnomad FIN

AF:

0.0889

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0947

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.0641

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0370

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0769

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0759

AC:

11540

AN:

152134

Hom.:

493

Cov.:

AF XY:

0.0749

AC XY:

5571

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0423

AC:

1756

AN:

41526

American (AMR)

AF:

0.0780

AC:

1191

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.0686

AC:

238

AN:

3470

East Asian (EAS)

AF:

0.0853

AC:

442

AN:

5184

South Asian (SAS)

AF:

0.0498

AC:

240

AN:

4816

European-Finnish (FIN)

AF:

0.0889

AC:

940

AN:

10570

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0946

AC:

6434

AN:

67990

Other (OTH)

AF:

0.100

AC:

211

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

525

1050

1575

2100

2625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0812

Hom.:

Bravo

AF:

0.0750

Asia WGS

AF:

0.0660

AC:

228

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.4

(source)

DANN

Benign

0.67

PhyloP100

0.61

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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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