8-1548923-C-G

Variant names:

• chr8-1548923-C-G
• rs1801653394
• NM_001346810.2:c.470C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001346810.2(DLGAP2):​c.470C>G​(p.Ser157Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,445,868 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DLGAP2 NM_001346810.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.48

Genes affected

DLGAP2 (HGNC:2906): (DLG associated protein 2) The product of this gene is a membrane-associated protein that may play a role in synapse organization and signalling in neuronal cells. This gene is biallelically expressed in the brain, however, only the paternal allele is expressed in the testis (PMID:18055845). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP2	NM_001346810.2	c.470C>G	p.Ser157Cys	missense_variant	Exon 5 of 15	ENST00000637795.2	NP_001333739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP2	ENST00000637795.2	c.470C>G	p.Ser157Cys	missense_variant	Exon 5 of 15	5	NM_001346810.2	ENSP00000489774.1
DLGAP2	ENST00000520901.5	c.278C>G	p.Ser93Cys	missense_variant	Exon 1 of 10	1		ENSP00000430563.3
DLGAP2	ENST00000421627.7	c.467C>G	p.Ser156Cys	missense_variant	Exon 5 of 15	5		ENSP00000400258.3
DLGAP2	ENST00000612087.1	c.230C>G	p.Ser77Cys	missense_variant	Exon 2 of 11	5		ENSP00000484215.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1445868 Hom.: 0 Cov.: 35 AF XY: 0.00000139 AC XY: 1 AN XY: 719686

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.230C>G (p.S77C) alteration is located in exon 2 (coding exon 1) of the DLGAP2 gene. This alteration results from a C to G substitution at nucleotide position 230, causing the serine (S) at amino acid position 77 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	.;M;.
PrimateAI	Uncertain	0.67	T
REVEL	Uncertain	0.34
Sift4G	Uncertain	0.013	.;.;D
Polyphen		1.0	.;D;.
Vest4		0.74
MutPred		0.21		.;Loss of disorder (P = 0.0416);.;
MVP		0.33
MPC		0.45
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.20
gMVP		0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs1801653394; hg19: chr8-1497089;