2-113942363-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005721.5(ACTR3):c.858+12dup variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,558,400 control chromosomes in the GnomAD database, including 53 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (36 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (17 hom.)
• Consequence: ACTR3 NM_005721.5 splice_donor_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.71

Genes affected

ACTR3 (HGNC:170): (actin related protein 3) The specific function of this gene has not yet been determined; however, the protein it encodes is known to be a major constituent of the ARP2/3 complex. This complex is located at the cell surface and is essential to cell shape and motility through lamellipodial actin assembly and protrusion. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-113942363-A-AT is Benign according to our data. Variant chr2-113942363-A-AT is described in ClinVar as [Benign]. Clinvar id is 783339.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1610/151826) while in subpopulation AFR AF= 0.0371 (1540/41472). AF 95% confidence interval is 0.0356. There are 36 homozygotes in gnomad4. There are 781 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1611 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTR3	NM_005721.5	c.858+12dup		splice_donor_region_variant, intron_variant		ENST00000263238.7
ACTR3	NM_001277140.1	c.705+12dup		splice_donor_region_variant, intron_variant
ACTR3	NR_102318.1	n.1079+12dup		splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTR3	ENST00000263238.7	c.858+12dup		splice_donor_region_variant, intron_variant		1	NM_005721.5	P1
ACTR3	ENST00000535589.3	c.705+12dup		splice_donor_region_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1611 AN: 151708 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00276

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000192

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00317 AC: 656 AN: 206910 Hom.: 12 AF XY: 0.00237 AC XY: 269 AN XY: 113424

Gnomad AFR exome AF: 0.0386

Gnomad AMR exome AF: 0.00340

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.000212

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000250

Gnomad OTH exome AF: 0.00108

GnomAD4 exome AF: 0.00103 AC: 1449 AN: 1406574 Hom.: 17 Cov.: 29 AF XY: 0.000892 AC XY: 624 AN XY: 699338

Gnomad4 AFR exome AF: 0.0356

Gnomad4 AMR exome AF: 0.00290

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000786

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.0000578

Gnomad4 NFE exome AF: 0.000128

Gnomad4 OTH exome AF: 0.00192

GnomAD4 genome AF: 0.0106 AC: 1610 AN: 151826 Hom.: 36 Cov.: 32 AF XY: 0.0105 AC XY: 781 AN XY: 74178

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.00269

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.00711

Bravo AF: 0.0118

Asia WGS AF: 0.00116 AC: 5 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

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: rs147159854; hg19: chr2-114699940;