10-114300246-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.586

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 -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 GnomAd at 2 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00345 AC: 525 AN: 152122 Hom.: 2 Cov.: 33

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.: 2 AF XY: 0.00325 AC XY: 442 AN XY: 135902

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.: 26 Cov.: 30 AF XY: 0.00464 AC XY: 3377 AN XY: 727240

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.: 2 Cov.: 33 AF XY: 0.00313 AC XY: 233 AN XY: 74434

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.: 0

Bravo AF: 0.00366

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00627

EpiControl AF: 0.00699

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

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

Other links and lift over

dbSNP: rs144048981; hg19: chr10-116060005;