18-3499352-C-T

Variant names:

• chr18-3499352-C-T
• rs2049809103
• NM_004746.4:c.2767G>A

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.2767G>A​(p.Gly923Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DLGAP1 NM_004746.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87
• 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]

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=0.1935705).

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.2767G>A	p.Gly923Ser	missense	Exon 13 of 13	NP_004737.2
	DLGAP1	NM_001398525.1		c.2797G>A	p.Gly933Ser	missense	Exon 14 of 14	NP_001385454.1
	DLGAP1	NM_001398526.1		c.2797G>A	p.Gly933Ser	missense	Exon 14 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.2767G>A	p.Gly923Ser	missense	Exon 13 of 13	ENSP00000316377.3	O14490-1
	DLGAP1	ENST00000400147.6	TSL:1	c.1861G>A	p.Gly621Ser	missense	Exon 10 of 10	ENSP00000383011.2	O14490-2
	DLGAP1	ENST00000515196.6	TSL:2	c.1933G>A	p.Gly645Ser	missense	Exon 11 of 11	ENSP00000445973.2	A0A0A0MTP4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Pathogenic	27
DANN	Benign	0.94
DEOGEN2	Benign	0.031	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.050
Sift	Benign	0.28	T
Sift4G	Benign	0.29	T
Polyphen		0.17	B
Vest4		0.15
MutPred		0.40		Gain of phosphorylation at G923 (P = 0.003)
MVP		0.64
MPC		1.9
ClinPred		0.92	D
GERP RS		4.4
Varity_R		0.31
gMVP		0.35

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: rs2049809103; hg19: chr18-3499350;