chr18-34755689-A-T

Variant names:

• chr18-34755689-A-T
• rs75850110
• NM_001386795.1:c.-1-287A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001386795.1(DTNA):​c.-1-287A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 374,824 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (106 hom., cov: 33)
  • Exomes 𝑓: 0.026 (147 hom.)
• Consequence: DTNA NM_001386795.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.349
• 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

DTNA-AS1 (HGNC:58208):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-34755689-A-T is Benign according to our data. Variant chr18-34755689-A-T is described in ClinVar as Benign. ClinVar VariationId is 1258003.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0261 (3981/152288) while in subpopulation NFE AF = 0.0341 (2321/68024). AF 95% confidence interval is 0.033. There are 106 homozygotes in GnomAd4. There are 2120 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3981 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.-1-287A>T		intron	N/A	NP_001373724.1	A0A7P0TBH9
	DTNA	NM_001386788.1		c.-1-287A>T		intron	N/A	NP_001373717.1	Q9Y4J8-17
	DTNA	NM_001198938.2		c.-1-287A>T		intron	N/A	NP_001185867.1	Q9Y4J8-15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNA	ENST00000444659.6	TSL:5 MANE Select	c.-1-287A>T		intron	N/A	ENSP00000405819.2	Q9Y4J8-17
	DTNA	ENST00000598334.5	TSL:1	c.-1-287A>T		intron	N/A	ENSP00000470152.1	Q9Y4J8-15
	DTNA	ENST00000399121.9	TSL:1	c.-1-287A>T		intron	N/A	ENSP00000382072.5	Q9Y4J8-14

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3982 AN: 152170 Hom.: 106 Cov.: 33

Gnomad AFR AF: 0.00502

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.0968

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.0215

GnomAD4 exome AF: 0.0257 AC: 5726 AN: 222536 Hom.: 147 AF XY: 0.0242 AC XY: 2898 AN XY: 119972

African (AFR) AF: 0.00472 AC: 32 AN: 6784

American (AMR) AF: 0.0133 AC: 131 AN: 9884

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 117 AN: 6164

East Asian (EAS) AF: 0.00 AC: 0 AN: 11658

South Asian (SAS) AF: 0.00616 AC: 209 AN: 33938

European-Finnish (FIN) AF: 0.0875 AC: 823 AN: 9404

Middle Eastern (MID) AF: 0.00794 AC: 7 AN: 882

European-Non Finnish (NFE) AF: 0.0311 AC: 4096 AN: 131844

Other (OTH) AF: 0.0260 AC: 311 AN: 11978

GnomAD4 genome AF: 0.0261 AC: 3981 AN: 152288 Hom.: 106 Cov.: 33 AF XY: 0.0285 AC XY: 2120 AN XY: 74466

African (AFR) AF: 0.00500 AC: 208 AN: 41576

American (AMR) AF: 0.0183 AC: 280 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00642 AC: 31 AN: 4828

European-Finnish (FIN) AF: 0.0968 AC: 1025 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0341 AC: 2321 AN: 68024

Other (OTH) AF: 0.0213 AC: 45 AN: 2114

Alfa AF: 0.0373 Hom.: 18

Bravo AF: 0.0183

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.78
PhyloP100		0.35
PromoterAI		-0.0034	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs75850110; hg19: chr18-32335653;