ENST00000598774.6:c.-127+62G>A

Variant names:

• chr18-34493576-G-A
• rs112193831
• ENST00000598774.6:c.-127+62G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000598774.6(DTNA):​c.-127+62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 151,202 control chromosomes in the GnomAD database, including 1,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1100 hom., cov: 30)
  • Exomes 𝑓: 0.085 (1 hom.)
• Consequence: DTNA ENST00000598774.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0630
• Publications: 0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 18-34493576-G-A is Benign according to our data. Variant chr18-34493576-G-A is described in ClinVar as Benign. ClinVar VariationId is 1291505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000598774.6. 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_001386754.1		c.-127+62G>A		intron	N/A	NP_001373683.1	A0A7P0Z4D7
	DTNA	NM_001386755.1		c.-127+62G>A		intron	N/A	NP_001373684.1	A0A7P0Z4D7
	DTNA	NM_001386760.1		c.-127+62G>A		intron	N/A	NP_001373689.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNA	ENST00000598774.6	TSL:1	c.-127+62G>A		intron	N/A	ENSP00000472031.1	Q9Y4J8-5
	DTNA	ENST00000315456.10	TSL:1	c.-127+62G>A		intron	N/A	ENSP00000322519.5	Q9Y4J8-7
	DTNA	ENST00000684266.1		c.-127+62G>A		intron	N/A	ENSP00000507106.1	A0A7P0Z4D7

Frequencies

GnomAD3 genomes AF: 0.106 AC: 15970 AN: 150860 Hom.: 1100 Cov.: 30

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0892

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.0877

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0894

GnomAD4 exome AF: 0.0855 AC: 20 AN: 234 Hom.: 1 AF XY: 0.0663 AC XY: 11 AN XY: 166

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.167 AC: 1 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0810 AC: 17 AN: 210

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.106 AC: 15974 AN: 150968 Hom.: 1100 Cov.: 30 AF XY: 0.112 AC XY: 8283 AN XY: 73700

African (AFR) AF: 0.0438 AC: 1807 AN: 41292

American (AMR) AF: 0.165 AC: 2515 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.0892 AC: 309 AN: 3464

East Asian (EAS) AF: 0.196 AC: 979 AN: 5006

South Asian (SAS) AF: 0.145 AC: 694 AN: 4782

European-Finnish (FIN) AF: 0.199 AC: 2051 AN: 10324

Middle Eastern (MID) AF: 0.0764 AC: 22 AN: 288

European-Non Finnish (NFE) AF: 0.106 AC: 7158 AN: 67596

Other (OTH) AF: 0.0885 AC: 186 AN: 2102

Alfa AF: 0.0544 Hom.: 68

Bravo AF: 0.100

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.8
DANN	Benign	0.96
PhyloP100		-0.063
PromoterAI		-0.0037	Neutral
RBP_binding_hub_radar		0.77
RBP_regulation_power_radar		3.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs112193831; hg19: chr18-32073540;