18-34710406-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001386795.1(DTNA):c.-41G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 152,286 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DTNA NM_001386795.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.46

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 18-34710406-G-C is Benign according to our data. Variant chr18-34710406-G-C is described in ClinVar as [Benign]. Clinvar id is 137174.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 183 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNA	NM_001386795.1	c.-41G>C		5_prime_UTR_variant	1/23	ENST00000444659.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNA	ENST00000444659.6	c.-41G>C		5_prime_UTR_variant	1/23	5	NM_001386795.1	P3

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 183 AN: 152168 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00427

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000958

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00120 AC: 183 AN: 152286 Hom.: 2 Cov.: 32 AF XY: 0.00119 AC XY: 89 AN XY: 74490

Gnomad4 AFR AF: 0.00426

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.00153 Hom.: 0

Bravo AF: 0.00158

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 17, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	19
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs540625328; hg19: chr18-32290370;