dbSNP rs352143: TWF2:p.Lys196Lys (chr3-52230891-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_007284.4(TWF2):c.588A>G(p.Lys196Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,609,484 control chromosomes in the GnomAD database, including 34,934 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 0.23 ( 4613 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30321 hom. )

Consequence

TWF2
NM_007284.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.557

Publications

56 publications found

Variant links:

Genes affected

TWF2 (HGNC:9621): (twinfilin actin binding protein 2) The protein encoded by this gene was identified by its interaction with the catalytic domain of protein kinase C-zeta. The encoded protein contains an actin-binding site and an ATP-binding site. It is most closely related to twinfilin (PTK9), a conserved actin monomer-binding protein. [provided by RefSeq, Jul 2008]

TWF2 links:

ENSG00000173366 (HGNC:):

ENSG00000173366 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.083).

BP7

Synonymous conserved (PhyloP=0.557 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TWF2	NM_007284.4 link	c.588A>G	p.Lys196Lys	synonymous_variant	Exon 6 of 9	ENST00000305533.10	NP_009215.1	Q6IBS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TWF2	ENST00000305533.10 link	c.588A>G	p.Lys196Lys	synonymous_variant	Exon 6 of 9	1	NM_007284.4	ENSP00000303908.4		Q6IBS0
ENSG00000173366	ENST00000494383.1 link	c.168A>G	p.Lys56Lys	synonymous_variant	Exon 2 of 5	2		ENSP00000417517.1		H0Y858

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34474

AN:

151444

Hom.:

4603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.361

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.0396

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.0924

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.239

GnomAD2 exomes

AF:

0.166

AC:

39993

AN:

241420

AF XY:

0.162

show subpopulations

Gnomad AFR exome

AF:

0.363

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.0326

Gnomad FIN exome

AF:

0.0971

Gnomad NFE exome

AF:

0.194

Gnomad OTH exome

AF:

0.176

GnomAD4 exome

AF:

0.197

AC:

286807

AN:

1457922

Hom.:

30321

Cov.:

AF XY:

0.194

AC XY:

140689

AN XY:

724910

show subpopulations

African (AFR)

AF:

0.378

AC:

12653

AN:

33434

American (AMR)

AF:

0.138

AC:

6100

AN:

44122

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

4440

AN:

26002

East Asian (EAS)

AF:

0.0284

AC:

1126

AN:

39626

South Asian (SAS)

AF:

0.129

AC:

11051

AN:

85742

European-Finnish (FIN)

AF:

0.103

AC:

5480

AN:

52974

Middle Eastern (MID)

AF:

0.181

AC:

1040

AN:

5756

European-Non Finnish (NFE)

AF:

0.210

AC:

232925

AN:

1110036

Other (OTH)

AF:

0.199

AC:

11992

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

13419

26838

40256

53675

67094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8114

16228

24342

32456

40570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.228

AC:

34529

AN:

151562

Hom.:

4613

Cov.:

AF XY:

0.219

AC XY:

16208

AN XY:

74048

show subpopulations

African (AFR)

AF:

0.362

AC:

14887

AN:

41166

American (AMR)

AF:

0.174

AC:

2660

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

598

AN:

3468

East Asian (EAS)

AF:

0.0391

AC:

200

AN:

5120

South Asian (SAS)

AF:

0.124

AC:

598

AN:

4810

European-Finnish (FIN)

AF:

0.0924

AC:

976

AN:

10560

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.203

AC:

13772

AN:

67866

Other (OTH)

AF:

0.240

AC:

505

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1161

2322

3483

4644

5805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.210

Hom.:

7484

Bravo

AF:

0.241

Asia WGS

AF:

0.106

AC:

371

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

3.6

(source)

DANN

Benign

0.75

PhyloP100

0.56

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=296/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over