8-1549189-C-G

Position:

• chr8-1549189-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001346810.2(DLGAP2):​c.736C>G​(p.Leu246Val) 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. 11/19 in silico tools predict a benign outcome for this variant. 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: 1.81

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32506293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP2	NM_001346810.2	c.736C>G	p.Leu246Val	missense_variant	5/15	ENST00000637795.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP2	ENST00000637795.2	c.736C>G	p.Leu246Val	missense_variant	5/15	5	NM_001346810.2
DLGAP2	ENST00000520901.5	c.547C>G	p.Leu183Val	missense_variant	1/10	1
DLGAP2	ENST00000421627.7	c.733C>G	p.Leu245Val	missense_variant	5/15	5
DLGAP2	ENST00000612087.1	c.496C>G	p.Leu166Val	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

Oct 03, 2022

The c.496C>G (p.L166V) 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 496, causing the leucine (L) at amino acid position 166 to be replaced by a valine (V). 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	0.26
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;D;T
Eigen	Benign	0.082
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Pathogenic	3.2	.;M;.
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.71	T
REVEL	Benign	0.20
Sift4G	Uncertain	0.0030	.;.;D
Polyphen		1.0	.;D;.
Vest4		0.85
MutPred		0.32		.;Gain of MoRF binding (P = 0.0799);.;
MVP		0.40
MPC		0.51
ClinPred		0.93	D
GERP RS		-0.11
Varity_R		0.14
gMVP		0.21

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: chr8-1497355;