chr18-3879263-A-T

Variant names:

• chr18-3879263-A-T
• rs2071083363
• NM_004746.4:c.806T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004746.4(DLGAP1):​c.806T>A​(p.Leu269Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DLGAP1 NM_004746.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.28

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]

DLGAP1-AS3 (HGNC:27317): (DLGAP1 antisense RNA 3)

LOC124904238 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15277404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.806T>A	p.Leu269Gln	missense_variant	Exon 4 of 13	ENST00000315677.8	NP_004737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.806T>A	p.Leu269Gln	missense_variant	Exon 4 of 13	5	NM_004746.4	ENSP00000316377.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

DLGAP1-related disorder Uncertain:1

May 22, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The DLGAP1 c.806T>A variant is predicted to result in the amino acid substitution p.Leu269Gln. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.096	T;.;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.033
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.8	N;.;.
REVEL	Benign	0.026
Sift	Benign	0.35	T;.;.
Sift4G	Benign	0.61	T;T;.
Polyphen		0.010	B;.;B
Vest4		0.50
MutPred		0.20		Gain of disorder (P = 0.0319);Gain of disorder (P = 0.0319);Gain of disorder (P = 0.0319);
MVP		0.24
MPC		0.40
ClinPred		0.50	T
GERP RS		5.5
Varity_R		0.21
gMVP		0.21

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: rs2071083363; hg19: chr18-3879263;