rs2071083363

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr18-3879263-A-T
• chr18-3879263-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004746.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	NM_004746.4	MANE Select	c.806T>A	p.Leu269Gln	missense	Exon 4 of 13	NP_004737.2
	DLGAP1	NM_001398525.1		c.806T>A	p.Leu269Gln	missense	Exon 4 of 14	NP_001385454.1
	DLGAP1	NM_001398526.1		c.806T>A	p.Leu269Gln	missense	Exon 4 of 14	NP_001385455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	ENST00000315677.8	TSL:5 MANE Select	c.806T>A	p.Leu269Gln	missense	Exon 4 of 13	ENSP00000316377.3	O14490-1
	DLGAP1	ENST00000498188.5	TSL:1	n.814T>A		non_coding_transcript_exon	Exon 1 of 5
	DLGAP1-AS3	ENST00000577649.1	TSL:1	n.112+972A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	DLGAP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.026
Sift	Benign	0.35	T
Sift4G	Benign	0.61	T
Polyphen		0.010	B
Vest4		0.50
MutPred		0.20		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
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs2071083363; hg19: chr18-3879263;