chr20-36526837-G-T

Variant names:

• chr20-36526837-G-T
• NM_001365621.2:c.2785G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The NM_001365621.2(DLGAP4):​c.2785G>T​(p.Val929Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,457,830 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: DLGAP4 NM_001365621.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93
• 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]

DLGAP4-AS1 (HGNC:51223): (DLGAP4 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.2785G>T	p.Val929Phe	missense	Exon 13 of 13	NP_001352550.1	Q9Y2H0-2
	DLGAP4	NM_014902.6		c.2776G>T	p.Val926Phe	missense	Exon 13 of 13	NP_055717.2
	DLGAP4	NM_183006.4		c.1168G>T	p.Val390Phe	missense	Exon 7 of 7	NP_892118.1	Q9Y2H0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP4	ENST00000339266.10	TSL:5 MANE Select	c.2785G>T	p.Val929Phe	missense	Exon 13 of 13	ENSP00000341633.5	Q9Y2H0-2
	DLGAP4	ENST00000373913.7	TSL:1	c.2776G>T	p.Val926Phe	missense	Exon 13 of 13	ENSP00000363023.3	Q9Y2H0-1
	DLGAP4	ENST00000340491.8	TSL:1	c.1168G>T	p.Val390Phe	missense	Exon 7 of 7	ENSP00000345700.4	Q9Y2H0-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1457830 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725064

African (AFR) AF: 0.00 AC: 0 AN: 33326

American (AMR) AF: 0.00 AC: 0 AN: 43874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 85820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4918

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110852

Other (OTH) AF: 0.00 AC: 0 AN: 60168

GnomAD4 genome Cov.: 31

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	Uncertain	0.50
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.55		Loss of MoRF binding (P = 0.0897)
MVP		0.60
MPC		1.7
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.43
gMVP		0.63
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr20-35155240; COSMIC: COSV59424597; COSMIC: COSV59424597;