chr18-34593487-G-C

Position:

• chr18-34593487-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The ENST00000598334.5(DTNA):​c.-178G>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 0.00473 in 152,266 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (7 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DTNA ENST00000598334.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.80

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 18-34593487-G-C is Benign according to our data. Variant chr18-34593487-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1704908.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 720 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNA	NM_001128175.2	c.-178G>C		5_prime_UTR_variant	1/12		NP_001121647.1
DTNA	NM_001198938.2	c.-178G>C		5_prime_UTR_variant	1/20		NP_001185867.1
DTNA	NM_001198939.2	c.-178G>C		5_prime_UTR_variant	1/22		NP_001185868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000399121.9	c.-178G>C		5_prime_UTR_variant	1/22	1		ENSP00000382072	A1
DTNA	ENST00000554864.7	c.-178G>C		5_prime_UTR_variant	1/12	1		ENSP00000451516	A1
DTNA	ENST00000595022.5	c.-178G>C		5_prime_UTR_variant	1/21	1		ENSP00000473078	A1

Frequencies

GnomAD3 genomes AF: 0.00473 AC: 719 AN: 152148 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0312

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00463

Gnomad OTH AF: 0.00191

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

GnomAD4 genome AF: 0.00473 AC: 720 AN: 152266 Hom.: 7 Cov.: 32 AF XY: 0.00575 AC XY: 428 AN XY: 74446

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0312

Gnomad4 NFE AF: 0.00465

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00566 Hom.: 0

Bravo AF: 0.00224

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 10, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs183120151; hg19: chr18-32173451;