18-3499206-G-A

Position:

• chr18-3499206-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_004746.4(DLGAP1):​c.2913C>T​(p.Pro971Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DLGAP1 NM_004746.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.133

Genes affected

DLGAP1 (HGNC:2905): (DLG associated protein 1) Predicted to enable molecular adaptor activity. Predicted to be a structural constituent of postsynaptic density. Predicted to be involved in several processes, including aggresome assembly; regulation of postsynaptic neurotransmitter receptor activity; and regulation of proteasomal protein catabolic process. Predicted to be located in plasma membrane. Predicted to be part of postsynaptic density. Predicted to be active in glutamatergic synapse and postsynaptic density, intracellular component. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 18-3499206-G-A is Benign according to our data. Variant chr18-3499206-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648533.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.133 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.2913C>T	p.Pro971Pro	synonymous_variant	13/13	ENST00000315677.8	NP_004737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.2913C>T	p.Pro971Pro	synonymous_variant	13/13	5	NM_004746.4	ENSP00000316377.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440698 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 715764

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

DLGAP1: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.95

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-3499204;