8-1549375-A-C

Variant summary

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

The NM_001346810.2(DLGAP2):c.922A>C(p.Thr308Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DLGAP2 NM_001346810.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.43

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/exons	MANE	UniProt
DLGAP2	NM_001346810.2	c.922A>C	p.Thr308Pro	missense_variant	5/15	ENST00000637795.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP2	ENST00000637795.2	c.922A>C	p.Thr308Pro	missense_variant	5/15	5	NM_001346810.2
DLGAP2	ENST00000520901.5	c.733A>C	p.Thr245Pro	missense_variant	1/10	1
DLGAP2	ENST00000421627.7	c.919A>C	p.Thr307Pro	missense_variant	5/15	5
DLGAP2	ENST00000612087.1	c.682A>C	p.Thr228Pro	missense_variant	2/11	5		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.682A>C (p.T228P) alteration is located in exon 2 (coding exon 1) of the DLGAP2 gene. This alteration results from a A to C substitution at nucleotide position 682, causing the threonine (T) at amino acid position 228 to be replaced by a proline (P). 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	0.11
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
Cadd	Pathogenic	27
Dann	Uncertain	0.99
DEOGEN2	Benign	0.072	T;T;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.50	D;D;D
MetaSVM	Benign	-0.51	T
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.55	T
Polyphen		1.0	.;D;.
Vest4		0.71
MutPred		0.17		.;Loss of phosphorylation at T307 (P = 0.0637);.;
MVP		0.43
MPC		0.58
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.69
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-1497541;