Variant 10-114297241-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001001936.3(AFAP1L2):c.2286C>T(p.His762=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0048 in 1,613,760 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 19 hom. )

Consequence

AFAP1L2
NM_001001936.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.81

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 10-114297241-G-A is Benign according to our data. Variant chr10-114297241-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640862.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.81 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFAP1L2	NM_001001936.3 linkuse as main transcript	c.2286C>T	p.His762=	synonymous_variant	17/19	ENST00000304129.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFAP1L2	ENST00000304129.9 linkuse as main transcript	c.2286C>T	p.His762=	synonymous_variant	17/19	1	NM_001001936.3	P4	Q8N4X5-1
AFAP1L2	ENST00000369271.7 linkuse as main transcript	c.2286C>T	p.His762=	synonymous_variant	17/19	1		A2	Q8N4X5-2
AFAP1L2	ENST00000696688.1 linkuse as main transcript	c.2370C>T	p.His790=	synonymous_variant	18/20			A2
AFAP1L2	ENST00000491814.1 linkuse as main transcript	n.1408C>T		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes

AF:

0.00351

AC:

533

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00133

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00608

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00372

AC:

932

AN:

250488

Hom.:

AF XY:

0.00387

AC XY:

524

AN XY:

135458

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.000796

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000984

Gnomad NFE exome

AF:

0.00702

Gnomad OTH exome

AF:

0.00295

GnomAD4 exome

AF:

0.00494

AC:

7221

AN:

1461666

Hom.:

Cov.:

AF XY:

0.00479

AC XY:

3485

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00203

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00609

Gnomad4 OTH exome

AF:

0.00358

GnomAD4 genome

AF:

0.00350

AC:

533

AN:

152094

Hom.:

Cov.:

AF XY:

0.00309

AC XY:

230

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00145

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00133

Gnomad4 NFE

AF:

0.00608

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00428

Hom.:

Bravo

AF:

0.00367

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00643

EpiControl

AF:

0.00747

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

AFAP1L2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.4

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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