10-114297241-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.81

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]

ACMG classification

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 GnomAd at 5 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 533 AN: 151980 Hom.: 5 Cov.: 32

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.: 4 AF XY: 0.00387 AC XY: 524 AN XY: 135458

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.: 19 Cov.: 36 AF XY: 0.00479 AC XY: 3485 AN XY: 727132

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.: 5 Cov.: 32 AF XY: 0.00309 AC XY: 230 AN XY: 74366

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.: 0

Bravo AF: 0.00367

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00643

EpiControl AF: 0.00747

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs140286473; hg19: chr10-116057000;