Variant rs621375 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001001936.3(AFAP1L2):c.621A>G(p.Lys207=) 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
AFAP1L2	NM_001001936.3 linkuse as main transcript	c.621A>G	p.Lys207=	synonymous_variant	7/19	ENST00000304129.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFAP1L2	ENST00000304129.9 linkuse as main transcript	c.621A>G	p.Lys207=	synonymous_variant	7/19	1	NM_001001936.3	P4	Q8N4X5-1
AFAP1L2	ENST00000369271.7 linkuse as main transcript	c.621A>G	p.Lys207=	synonymous_variant	7/19	1		A2	Q8N4X5-2
AFAP1L2	ENST00000696688.1 linkuse as main transcript	c.705A>G	p.Lys235=	synonymous_variant	8/20			A2
AFAP1L2	ENST00000419268.1 linkuse as main transcript	c.675A>G	p.Lys225=	synonymous_variant	8/9	5

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

GnomAD3 exomes

AF:

0.224

AC:

56110

AN:

250406

Hom.:

8560

AF XY:

0.226

AC XY:

30543

AN XY:

135276

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 SAS exome

AF:

0.353

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

Gnomad4 AFR exome

AF:

0.655

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.150

Gnomad4 SAS exome

AF:

0.348

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.181

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.315

AC:

47853

AN:

151904

Hom.:

10875

Cov.:

AF XY:

0.312

AC XY:

23142

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.645

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.280

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.353

Gnomad4 FIN

AF:

0.162

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.278

Alfa

AF:

0.223

Hom.:

6689

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

DANN

Benign

0.71

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over