dbSNP rs621375: AFAP1L2:p.Lys207Lys (chr10-114314042-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_001001936.3(AFAP1L2):c.621A>G(p.Lys207Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,608,964 control chromosomes in the GnomAD database, including 46,353 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 0.32 ( 10875 hom., cov: 32)

Exomes 𝑓: 0.20 ( 35478 hom. )

Consequence

AFAP1L2
NM_001001936.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.472

Publications

15 publications found

Variant links:

Genes affected

AFAP1L2 (HGNC:25901): (actin filament associated protein 1 like 2) Enables SH2 domain binding activity; SH3 domain binding activity; and protein tyrosine kinase activator activity. Involved in several processes, including positive regulation of epidermal growth factor receptor signaling pathway; regulation of gene expression; and regulation of mitotic cell cycle. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

AFAP1L2 links:

ENSG00000299554 (HGNC:):

ENSG00000299554 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 (BayesDel_noAF=-0.45).

BP7

Synonymous conserved (PhyloP=0.472 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFAP1L2	NM_001001936.3 link	c.621A>G	p.Lys207Lys	synonymous_variant	Exon 7 of 19	ENST00000304129.9	NP_001001936.1	Q8N4X5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFAP1L2	ENST00000304129.9 link	c.621A>G	p.Lys207Lys	synonymous_variant	Exon 7 of 19	1	NM_001001936.3	ENSP00000303042.4		Q8N4X5-1

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47779

AN:

151786

Hom.:

10849

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.276

GnomAD2 exomes

AF:

0.224

AC:

56110

AN:

250406

AF XY:

0.226

show subpopulations

Gnomad AFR exome

AF:

0.647

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.280

Gnomad EAS exome

AF:

0.0840

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.203

AC:

296204

AN:

1457060

Hom.:

35478

Cov.:

AF XY:

0.207

AC XY:

149704

AN XY:

723828

show subpopulations

African (AFR)

AF:

0.655

AC:

21888

AN:

33424

American (AMR)

AF:

0.162

AC:

7210

AN:

44574

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

7091

AN:

26058

East Asian (EAS)

AF:

0.150

AC:

5943

AN:

39550

South Asian (SAS)

AF:

0.348

AC:

29949

AN:

86072

European-Finnish (FIN)

AF:

0.154

AC:

8221

AN:

53360

Middle Eastern (MID)

AF:

0.302

AC:

1735

AN:

5744

European-Non Finnish (NFE)

AF:

0.181

AC:

200113

AN:

1108090

Other (OTH)

AF:

0.234

AC:

14054

AN:

60188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

10829

21658

32488

43317

54146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7380

14760

22140

29520

36900

<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:

0.315

AC:

47853

AN:

151904

Hom.:

10875

Cov.:

AF XY:

0.312

AC XY:

23142

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.645

AC:

26730

AN:

41438

American (AMR)

AF:

0.195

AC:

2979

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

972

AN:

3468

East Asian (EAS)

AF:

0.110

AC:

564

AN:

5144

South Asian (SAS)

AF:

0.353

AC:

1694

AN:

4804

European-Finnish (FIN)

AF:

0.162

AC:

1707

AN:

10538

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12374

AN:

67940

Other (OTH)

AF:

0.278

AC:

584

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1336

2672

4008

5344

6680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.227

Hom.:

8893

Bravo

AF:

0.328

Asia WGS

AF:

0.284

AC:

988

AN:

3478

EpiCase

AF:

0.191

EpiControl

AF:

0.194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

5.2

(source)

DANN

Benign

0.71

PhyloP100

0.47

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over