chr20-36432527-G-C

Position:

• chr20-36432527-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001365621.2(DLGAP4):​c.810G>C​(p.Pro270Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0040 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DLGAP4 NM_001365621.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.41

Genes affected

DLGAP4 (HGNC:24476): (DLG associated protein 4) The product of this gene is a membrane-associated guanylate kinase found at the postsynaptic density in neuronal cells. It is a signaling molecule that can interact with potassium channels and receptors, as well as other signaling molecules. The protein encoded by this gene can interact with PSD-95 through its guanylate kinase domain and may be involved in clustering PSD-95 in the postsynaptic density region. The encoded protein is one of at least four similar proteins that have been found. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-36432527-G-C is Benign according to our data. Variant chr20-36432527-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 751115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.41 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP4	NM_001365621.2	c.810G>C	p.Pro270Pro	synonymous_variant	3/13	ENST00000339266.10	NP_001352550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP4	ENST00000339266.10	c.810G>C	p.Pro270Pro	synonymous_variant	3/13	5	NM_001365621.2	ENSP00000341633.5
DLGAP4	ENST00000373913.7	c.810G>C	p.Pro270Pro	synonymous_variant	3/13	1		ENSP00000363023.3
DLGAP4	ENST00000373907.6	c.810G>C	p.Pro270Pro	synonymous_variant	2/12	5		ENSP00000363014.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 305 AN: 134278 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00123

Gnomad AMR AF: 0.00173

Gnomad ASJ AF: 0.00189

Gnomad EAS AF: 0.00754

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.00668

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00155

Gnomad OTH AF: 0.00218

GnomAD3 exomes AF: 0.0000296 AC: 7 AN: 236832 Hom.: 0 AF XY: 0.0000385 AC XY: 5 AN XY: 129986

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000236

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00403 AC: 2100 AN: 520808 Hom.: 0 Cov.: 29 AF XY: 0.00348 AC XY: 978 AN XY: 280648

Gnomad4 AFR exome AF: 0.00287

Gnomad4 AMR exome AF: 0.000220

Gnomad4 ASJ exome AF: 0.00140

Gnomad4 EAS exome AF: 0.00118

Gnomad4 SAS exome AF: 0.00143

Gnomad4 FIN exome AF: 0.000222

Gnomad4 NFE exome AF: 0.00576

Gnomad4 OTH exome AF: 0.00366

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00227 AC: 305 AN: 134384 Hom.: 0 Cov.: 31 AF XY: 0.00242 AC XY: 158 AN XY: 65186

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00173

Gnomad4 ASJ AF: 0.00189

Gnomad4 EAS AF: 0.00755

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.00668

Gnomad4 NFE AF: 0.00155

Gnomad4 OTH AF: 0.00216

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.040
DANN	Benign	0.34

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: rs763627689; hg19: chr20-35060930;