chr18-34755980-A-T

Position:

• chr18-34755980-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001386795.1(DTNA):​c.4A>T​(p.Ile2Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DTNA NM_001386795.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.34

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNA	NM_001386795.1	c.4A>T	p.Ile2Phe	missense_variant	2/23	ENST00000444659.6	NP_001373724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000444659.6	c.4A>T	p.Ile2Phe	missense_variant	2/23	5	NM_001386795.1	ENSP00000405819	P3
	ENST00000596954.1	n.314-345T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Left ventricular noncompaction 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;T;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D;D;.;D;D;D;D;.;D;D;D;.
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.52	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.1	M;M;M;.;.;.;M;.;M;M;M;M;M;M;M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.1	N;.;N;.;.;.;.;.;N;N;.;.;.;N;.;N;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D;.;D;.;.;.;.;.;D;D;.;.;.;D;.;D;D
Sift4G	Uncertain	0.011	D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D;D
Polyphen		1.0	D;.;D;.;.;.;.;.;.;.;.;D;D;D;.;D;D
Vest4		0.82
MutPred		0.12		Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);Loss of MoRF binding (P = 0.0851);
MVP		0.50
MPC		1.3
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.39
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-32335944;