rs117571555

Variant names:

• chr18-34794098-G-A
• rs117571555
• NM_001386795.1:c.210G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001386795.1(DTNA):​c.210G>A​(p.Leu70Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00742 in 1,614,098 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (59 hom.)
• Consequence: DTNA NM_001386795.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 6.88
• Publications: 4 publications found

Genes affected

DTNA (HGNC:3057): (dystrobrevin alpha) The protein encoded by this gene belongs to the dystrobrevin subfamily of the dystrophin family. This protein is a component of the dystrophin-associated protein complex (DPC), which consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Mutations in this gene are associated with left ventricular noncompaction with congenital heart defects. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DTNA Gene-Disease associations (from GenCC):

• left ventricular noncompaction 1

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Meniere disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 18-34794098-G-A is Benign according to our data. Variant chr18-34794098-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 36029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 666 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386795.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNA	NM_001386795.1	MANE Select	c.210G>A	p.Leu70Leu	synonymous	Exon 4 of 23	NP_001373724.1	A0A7P0TBH9
	DTNA	NM_001386788.1		c.210G>A	p.Leu70Leu	synonymous	Exon 4 of 23	NP_001373717.1	Q9Y4J8-17
	DTNA	NM_001390.5		c.210G>A	p.Leu70Leu	synonymous	Exon 3 of 22	NP_001381.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNA	ENST00000444659.6	TSL:5 MANE Select	c.210G>A	p.Leu70Leu	synonymous	Exon 4 of 23	ENSP00000405819.2	Q9Y4J8-17
	DTNA	ENST00000598334.5	TSL:1	c.210G>A	p.Leu70Leu	synonymous	Exon 5 of 20	ENSP00000470152.1	Q9Y4J8-15
	DTNA	ENST00000399121.9	TSL:1	c.210G>A	p.Leu70Leu	synonymous	Exon 5 of 22	ENSP00000382072.5	Q9Y4J8-14

Frequencies

GnomAD3 genomes AF: 0.00438 AC: 667 AN: 152160 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00808

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00447 AC: 1124 AN: 251194 AF XY: 0.00478

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000971

Gnomad NFE exome AF: 0.00857

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00773 AC: 11304 AN: 1461820 Hom.: 59 Cov.: 32 AF XY: 0.00742 AC XY: 5396 AN XY: 727198

African (AFR) AF: 0.00143 AC: 48 AN: 33478

American (AMR) AF: 0.00139 AC: 62 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.000383 AC: 10 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39686

South Asian (SAS) AF: 0.00160 AC: 138 AN: 86252

European-Finnish (FIN) AF: 0.00103 AC: 55 AN: 53412

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5766

European-Non Finnish (NFE) AF: 0.00961 AC: 10687 AN: 1111996

Other (OTH) AF: 0.00485 AC: 293 AN: 60394

GnomAD4 genome AF: 0.00437 AC: 666 AN: 152278 Hom.: 2 Cov.: 32 AF XY: 0.00412 AC XY: 307 AN XY: 74452

African (AFR) AF: 0.00180 AC: 75 AN: 41558

American (AMR) AF: 0.00137 AC: 21 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.000660 AC: 7 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00807 AC: 549 AN: 68024

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00683 Hom.: 1

Bravo AF: 0.00437

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Left ventricular noncompaction 1 (4)
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.8
DANN	Benign	0.80
PhyloP100		6.9
Mutation Taster		=3/97	disease causing

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

Other links and lift over

dbSNP: rs117571555; hg19: chr18-32374062;