19-57154453-AG-A

Position:

• chr19-57154453-AG-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001012729.2(DUXA):​c.573delC​(p.Phe192fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,613,778 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (19 hom.)
• Consequence: DUXA NM_001012729.2 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.623

Genes affected

DUXA (HGNC:32179): (double homeobox A) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the DUXA homeobox gene family. Evidence of mRNA expression has not yet been found for this gene. Multiple, related processed pseudogenes have been found which are thought to reflect expression of this gene in the germ line or embryonic cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 19-57154453-AG-A is Benign according to our data. Variant chr19-57154453-AG-A is described in ClinVar as [Benign]. Clinvar id is 773778.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUXA	NM_001012729.2	c.573delC	p.Phe192fs	frameshift_variant	6/6	ENST00000554048.3	NP_001012747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUXA	ENST00000554048.3	c.573delC	p.Phe192fs	frameshift_variant	6/6	3	NM_001012729.2	ENSP00000452398.1

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 590 AN: 152190 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00659

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00644

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00414 AC: 1042 AN: 251420 Hom.: 8 AF XY: 0.00412 AC XY: 560 AN XY: 135896

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00693

Gnomad NFE exome AF: 0.00621

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00444 AC: 6495 AN: 1461470 Hom.: 19 Cov.: 31 AF XY: 0.00435 AC XY: 3166 AN XY: 727054

Gnomad4 AFR exome AF: 0.000807

Gnomad4 AMR exome AF: 0.00349

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.00573

Gnomad4 NFE exome AF: 0.00516

Gnomad4 OTH exome AF: 0.00359

GnomAD4 genome AF: 0.00387 AC: 590 AN: 152308 Hom.: 5 Cov.: 32 AF XY: 0.00369 AC XY: 275 AN XY: 74492

Gnomad4 AFR AF: 0.000986

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00659

Gnomad4 NFE AF: 0.00644

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00116 Hom.: 1

Bravo AF: 0.00324

EpiCase AF: 0.00540

EpiControl AF: 0.00504

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

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: rs151293806; hg19: chr19-57665821;