Variant 14-34711567-AAAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_138638.5(CFL2):c.*1295_*1297del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 454,326 control chromosomes in the GnomAD database, including 55 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 24 hom., cov: 33)

Exomes 𝑓: 0.011 ( 31 hom. )

Consequence

CFL2
NM_138638.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.41

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 14-34711567-AAAG-A is Benign according to our data. Variant chr14-34711567-AAAG-A is described in ClinVar as [Benign]. Clinvar id is 313084.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0139 (2121/152314) while in subpopulation AFR AF= 0.0172 (715/41562). AF 95% confidence interval is 0.0162. There are 24 homozygotes in gnomad4. There are 1021 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFL2	NM_138638.5 linkuse as main transcript	c.1295_1297del		3_prime_UTR_variant	4/4	ENST00000298159.11	NP_619579.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFL2	ENST00000298159.11 linkuse as main transcript	c.1295_1297del	3_prime_UTR_variant	4/4	1	NM_138638.5	ENSP00000298159	P1	Q9Y281-1
CFL2	ENST00000341223.8 linkuse as main transcript	c.1295_1297del	3_prime_UTR_variant	4/4	1		ENSP00000340635	P1	Q9Y281-1
CFL2	ENST00000672517.1 linkuse as main transcript	c.1295_1297del	3_prime_UTR_variant	5/5			ENSP00000500532	P1	Q9Y281-1

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2117

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.0138

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0110

AC:

1498

AN:

136478

Hom.:

AF XY:

0.0105

AC XY:

779

AN XY:

74096

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.0133

Gnomad ASJ exome

AF:

0.00602

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00627

Gnomad FIN exome

AF:

0.0201

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.0188

GnomAD4 exome

AF:

0.0113

AC:

3420

AN:

302012

Hom.:

AF XY:

0.0108

AC XY:

1857

AN XY:

172120

show subpopulations

Gnomad4 AFR exome

AF:

0.0170

Gnomad4 AMR exome

AF:

0.0137

Gnomad4 ASJ exome

AF:

0.00557

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00609

Gnomad4 FIN exome

AF:

0.0199

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.0130

GnomAD4 genome

AF:

0.0139

AC:

2121

AN:

152314

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1021

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0172

Gnomad4 AMR

AF:

0.0171

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.0138

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0110

Hom.:

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Nemaline Myopathy, Recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over