14-55151828-A-C

Position:

• chr14-55151828-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014750.5(DLGAP5):​c.2235T>G​(p.Ile745Met) 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. 15/21 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: DLGAP5 NM_014750.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0570

Genes affected

DLGAP5 (HGNC:16864): (DLG associated protein 5) Predicted to enable microtubule binding activity. Predicted to be involved in several processes, including centrosome localization; kinetochore assembly; and mitotic spindle organization. Located in several cellular components, including centrosome; cytosol; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

DLGAP5 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059634596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP5	NM_014750.5	c.2235T>G	p.Ile745Met	missense_variant	17/19	ENST00000247191.7	NP_055565.3
DLGAP5	NM_001146015.2	c.2235T>G	p.Ile745Met	missense_variant	17/20		NP_001139487.1
DLGAP5	XM_017021840.3	c.2235T>G	p.Ile745Met	missense_variant	17/19		XP_016877329.1
DLGAP5	XM_047432016.1	c.2235T>G	p.Ile745Met	missense_variant	17/20		XP_047287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP5	ENST00000247191.7	c.2235T>G	p.Ile745Met	missense_variant	17/19	1	NM_014750.5	ENSP00000247191.2
DLGAP5	ENST00000395425.6	c.2235T>G	p.Ile745Met	missense_variant	17/20	1		ENSP00000378815.2
DLGAP5	ENST00000554007.1	n.169T>G		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Jan 26, 2023

The c.2235T>G (p.I745M) alteration is located in exon 17 (coding exon 16) of the DLGAP5 gene. This alteration results from a T to G substitution at nucleotide position 2235, causing the isoleucine (I) at amino acid position 745 to be replaced by a methionine (M). 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	0.091
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.063	.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.28	N;N
REVEL	Benign	0.043
Sift	Benign	0.062	T;T
Sift4G	Uncertain	0.022	D;D
Polyphen		0.070	.;B
Vest4		0.12
MutPred		0.23		Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP		0.14
MPC		0.066
ClinPred		0.094	T
GERP RS		0.70
Varity_R		0.043
gMVP		0.061

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: chr14-55618546;