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GeneBe

10-114297337-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001001936.3(AFAP1L2):c.2190C>T(p.Arg730=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,613,864 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

AFAP1L2
NM_001001936.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.66
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-114297337-G-A is Benign according to our data. Variant chr10-114297337-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 773541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.66 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AFAP1L2NM_001001936.3 linkuse as main transcriptc.2190C>T p.Arg730= synonymous_variant 17/19 ENST00000304129.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AFAP1L2ENST00000304129.9 linkuse as main transcriptc.2190C>T p.Arg730= synonymous_variant 17/191 NM_001001936.3 P4Q8N4X5-1
AFAP1L2ENST00000369271.7 linkuse as main transcriptc.2190C>T p.Arg730= synonymous_variant 17/191 A2Q8N4X5-2
AFAP1L2ENST00000696688.1 linkuse as main transcriptc.2274C>T p.Arg758= synonymous_variant 18/20 A2
AFAP1L2ENST00000491814.1 linkuse as main transcriptn.1312C>T non_coding_transcript_exon_variant 5/62

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00109
AC:
166
AN:
152188
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00376
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000351
AC:
88
AN:
250864
Hom.:
0
AF XY:
0.000310
AC XY:
42
AN XY:
135636
show subpopulations
Gnomad AFR exome
AF:
0.00406
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.000281
Gnomad NFE exome
AF:
0.0000793
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000206
AC:
301
AN:
1461558
Hom.:
0
Cov.:
35
AF XY:
0.000175
AC XY:
127
AN XY:
727102
show subpopulations
Gnomad4 AFR exome
AF:
0.00505
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.000282
Gnomad4 NFE exome
AF:
0.0000585
Gnomad4 OTH exome
AF:
0.000497
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00109
AC:
166
AN:
152306
Hom.:
1
Cov.:
33
AF XY:
0.00105
AC XY:
78
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.00375
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000565
Hom.:
0
Bravo
AF:
0.00127
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023AFAP1L2: BP4, BP7 -
Benign, criteria provided, single submitterclinical testingInvitaeAug 08, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
Cadd
Benign
0.18
Dann
Benign
0.73

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.

Other links and lift over

dbSNP: rs115650575; hg19: chr10-116057096; COSMIC: COSV58417679; COSMIC: COSV58417679; API