20-36432372-C-G

Variant names:

• chr20-36432372-C-G
• NM_001365621.2:c.655C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001365621.2(DLGAP4):​c.655C>G​(p.Arg219Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DLGAP4 NM_001365621.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.69
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3016554).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365621.2. 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
	DLGAP4	NM_001365621.2	MANE Select	c.655C>G	p.Arg219Gly	missense	Exon 3 of 13	NP_001352550.1	Q9Y2H0-2
	DLGAP4	NM_014902.6		c.655C>G	p.Arg219Gly	missense	Exon 3 of 13	NP_055717.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP4	ENST00000339266.10	TSL:5 MANE Select	c.655C>G	p.Arg219Gly	missense	Exon 3 of 13	ENSP00000341633.5	Q9Y2H0-2
	DLGAP4	ENST00000373913.7	TSL:1	c.655C>G	p.Arg219Gly	missense	Exon 3 of 13	ENSP00000363023.3	Q9Y2H0-1
	DLGAP4	ENST00000373907.6	TSL:5	c.655C>G	p.Arg219Gly	missense	Exon 2 of 12	ENSP00000363014.2	Q9Y2H0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Benign	0.13	T
Sift4G	Benign	0.18	T
Polyphen		0.99	D
Vest4		0.41
MutPred		0.32		Loss of sheet (P = 0.0181)
MVP		0.42
MPC		0.70
ClinPred		0.72	D
GERP RS		4.1
Varity_R		0.20
gMVP		0.43
Mutation Taster		=65/35	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

hg19: chr20-35060775;