2-172102267-T-A

Position:

• chr2-172102267-T-A

Variant summary

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

The NM_004405.4(DLX2):​c.272A>T​(p.Gln91Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DLX2 NM_004405.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.63

Genes affected

DLX2 (HGNC:2915): (distal-less homeobox 2) Many vertebrate homeo box-containing genes have been identified on the basis of their sequence similarity with Drosophila developmental genes. Members of the Dlx gene family contain a homeobox that is related to that of Distal-less (Dll), a gene expressed in the head and limbs of the developing fruit fly. The Distal-less (Dlx) family of genes comprises at least 6 different members, DLX1-DLX6. The DLX proteins are postulated to play a role in forebrain and craniofacial development. This gene is located in a tail-to-tail configuration with another member of the gene family on the long arm of chromosome 2. [provided by RefSeq, Jul 2008]

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	Protein	UniProt
DLX2	NM_004405.4	c.272A>T	p.Gln91Leu	missense_variant	1/3	ENST00000234198.9	NP_004396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX2	ENST00000234198.9	c.272A>T	p.Gln91Leu	missense_variant	1/3	1	NM_004405.4	ENSP00000234198.4
DLX2	ENST00000466293.2	c.272A>T	p.Gln91Leu	missense_variant	1/2	2		ENSP00000446904.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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 09, 2024

The c.272A>T (p.Q91L) alteration is located in exon 1 (coding exon 1) of the DLX2 gene. This alteration results from a A to T substitution at nucleotide position 272, causing the glutamine (Q) at amino acid position 91 to be replaced by a leucine (L). 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	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.65	T;T
M_CAP	Pathogenic	0.61	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Pathogenic	0.84
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.29	T;T
Polyphen		0.97	D;.
Vest4		0.48
MutPred		0.38		Loss of disorder (P = 0.0323);Loss of disorder (P = 0.0323);
MVP		0.98
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.77
gMVP		0.71

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: chr2-172966995;