chr18-34679369-A-T

Position:

• chr18-34679369-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000598334.5(DTNA):​c.-126-99A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0611 in 152,290 control chromosomes in the GnomAD database, including 931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (931 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DTNA ENST00000598334.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.976

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 18-34679369-A-T is Benign according to our data. Variant chr18-34679369-A-T is described in ClinVar as [Benign]. Clinvar id is 1271976.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNA	NM_001128175.2	c.-126-99A>T		intron_variant
DTNA	NM_001198938.2	c.-126-99A>T		intron_variant
DTNA	NM_001198939.2	c.-126-99A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNA	ENST00000315456.10	c.-126-99A>T		intron_variant		1		A1
DTNA	ENST00000399121.9	c.-126-99A>T		intron_variant		1		A1
DTNA	ENST00000554864.7	c.-126-99A>T		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9248 AN: 152172 Hom.: 918 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00248

Gnomad OTH AF: 0.0372

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0611 AC: 9299 AN: 152290 Hom.: 931 Cov.: 32 AF XY: 0.0601 AC XY: 4472 AN XY: 74466

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.0197

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00248

Gnomad4 OTH AF: 0.0378

Alfa AF: 0.0397 Hom.: 81

Bravo AF: 0.0698

Asia WGS AF: 0.0200 AC: 70 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.32
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3875084; hg19: chr18-32259333;