10-77805813-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004747.4(DLG5):c.5016T>C(p.Asp1672=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,614,148 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0037 (18 hom.)
• Consequence: DLG5 NM_004747.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.820

Genes affected

DLG5 (HGNC:2904): (discs large MAGUK scaffold protein 5) This gene encodes a member of the family of discs large (DLG) homologs, a subset of the membrane-associated guanylate kinase (MAGUK) superfamily. The MAGUK proteins are composed of a catalytically inactive guanylate kinase domain, in addition to PDZ and SH3 domains, and are thought to function as scaffolding molecules at sites of cell-cell contact. The protein encoded by this gene localizes to the plasma membrane and cytoplasm, and interacts with components of adherens junctions and the cytoskeleton. It is proposed to function in the transmission of extracellular signals to the cytoskeleton and in the maintenance of epithelial cell structure. Alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-77805813-A-G is Benign according to our data. Variant chr10-77805813-A-G is described in ClinVar as [Benign]. Clinvar id is 718501.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.82 with no splicing effect.
• BS2: High AC in GnomAd at 286 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG5	NM_004747.4	c.5016T>C	p.Asp1672=	synonymous_variant	27/32	ENST00000372391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG5	ENST00000372391.7	c.5016T>C	p.Asp1672=	synonymous_variant	27/32	1	NM_004747.4	P1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152202 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00344

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00215 AC: 539 AN: 251274 Hom.: 2 AF XY: 0.00217 AC XY: 295 AN XY: 135794

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.000868

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.000739

Gnomad NFE exome AF: 0.00384

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00371 AC: 5428 AN: 1461828 Hom.: 18 Cov.: 31 AF XY: 0.00367 AC XY: 2667 AN XY: 727204

Gnomad4 AFR exome AF: 0.000597

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.00233

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.000974

Gnomad4 NFE exome AF: 0.00456

Gnomad4 OTH exome AF: 0.00270

GnomAD4 genome AF: 0.00188 AC: 286 AN: 152320 Hom.: 2 Cov.: 33 AF XY: 0.00152 AC XY: 113 AN XY: 74484

Gnomad4 AFR AF: 0.000577

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00344

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00240 Hom.: 1

Bravo AF: 0.00211

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00267

EpiControl AF: 0.00255

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

Invitae

Apr 03, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.24
Dann	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs41274580; hg19: chr10-79565571; COSMIC: COSV64948577; COSMIC: COSV64948577;