chr18-3879209-C-G

Variant names:

• chr18-3879209-C-G
• rs572366902
• NM_004746.4:c.860G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_004746.4(DLGAP1):​c.860G>C​(p.Arg287Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000993 in 1,410,540 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R287Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000099 (0 hom.)
• Consequence: DLGAP1 NM_004746.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.81
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 14 AD gene.

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.860G>C	p.Arg287Pro	missense	Exon 4 of 13	NP_004737.2
	DLGAP1	NM_001398525.1		c.860G>C	p.Arg287Pro	missense	Exon 4 of 14	NP_001385454.1
	DLGAP1	NM_001398526.1		c.860G>C	p.Arg287Pro	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.860G>C	p.Arg287Pro	missense	Exon 4 of 13	ENSP00000316377.3	O14490-1
	DLGAP1	ENST00000498188.5	TSL:1	n.868G>C		non_coding_transcript_exon	Exon 1 of 5
	DLGAP1-AS3	ENST00000577649.1	TSL:1	n.112+918C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000472 AC: 1 AN: 211976 AF XY: 0.00000882

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000102

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000993 AC: 14 AN: 1410540 Hom.: 0 Cov.: 31 AF XY: 0.0000101 AC XY: 7 AN XY: 696222

African (AFR) AF: 0.00 AC: 0 AN: 31758

American (AMR) AF: 0.00 AC: 0 AN: 37156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22818

East Asian (EAS) AF: 0.00 AC: 0 AN: 39156

South Asian (SAS) AF: 0.00 AC: 0 AN: 77810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5486

European-Non Finnish (NFE) AF: 0.0000120 AC: 13 AN: 1086592

Other (OTH) AF: 0.0000172 AC: 1 AN: 58008

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.35
Sift	Benign	0.037	D
Sift4G	Uncertain	0.047	D
Polyphen		0.058	B
Vest4		0.97
MutPred		0.40		Loss of MoRF binding (P = 0.0019)
MVP		0.74
MPC		1.4
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.66
gMVP		0.70
Mutation Taster		=35/65	disease causing

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: rs572366902; hg19: chr18-3879209;