Variant 10-114300246-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001001936.3(AFAP1L2):c.1905C>G(p.Thr635=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,614,124 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 26 hom. )

Consequence

AFAP1L2
NM_001001936.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.586

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-114300246-G-C is Benign according to our data. Variant chr10-114300246-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2640863.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.586 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFAP1L2	NM_001001936.3 linkuse as main transcript	c.1905C>G	p.Thr635=	synonymous_variant	15/19	ENST00000304129.9	NP_001001936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFAP1L2	ENST00000304129.9 linkuse as main transcript	c.1905C>G	p.Thr635=	synonymous_variant	15/19	1	NM_001001936.3	ENSP00000303042	P4	Q8N4X5-1
AFAP1L2	ENST00000369271.7 linkuse as main transcript	c.1905C>G	p.Thr635=	synonymous_variant	15/19	1		ENSP00000358276	A2	Q8N4X5-2
AFAP1L2	ENST00000696688.1 linkuse as main transcript	c.1989C>G	p.Thr663=	synonymous_variant	16/20			ENSP00000512810	A2
AFAP1L2	ENST00000491814.1 linkuse as main transcript	n.1027C>G		non_coding_transcript_exon_variant	3/6	2

Frequencies

GnomAD3 genomes

AF:

0.00345

AC:

525

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00547

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00313

AC:

786

AN:

251466

Hom.:

AF XY:

0.00325

AC XY:

442

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00533

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00472

AC:

6906

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00464

AC XY:

3377

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00109

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00571

Gnomad4 OTH exome

AF:

0.00394

GnomAD4 genome

AF:

0.00345

AC:

525

AN:

152240

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

233

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00547

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00465

Hom.:

Bravo

AF:

0.00366

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00627

EpiControl

AF:

0.00699

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

Aug 01, 2022

AFAP1L2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.2

DANN

Benign

0.31

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