Variant 2-172100890-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004405.4(DLX2):c.640G>A(p.Gly214Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,570 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

DLX2
NM_004405.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.99

Variant links:

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]

DLX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.640G>A	p.Gly214Ser	missense_variant	3/3	ENST00000234198.9	NP_004396.1	Q07687-1Q53QU7X5D7D8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX2	ENST00000234198.9 linkuse as main transcript	c.640G>A	p.Gly214Ser	missense_variant	3/3	1	NM_004405.4	ENSP00000234198.4		Q07687-1
DLX2	ENST00000466293.2 linkuse as main transcript	c.*503G>A		3_prime_UTR_variant	2/2	2		ENSP00000446904.1		Q07687-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247484

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134722

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460570

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726654

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2022

The c.640G>A (p.G214S) alteration is located in exon 3 (coding exon 3) of the DLX2 gene. This alteration results from a G to A substitution at nucleotide position 640, causing the glycine (G) at amino acid position 214 to be replaced by a serine (S). 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

Pathogenic

0.75

BayesDel_addAF

Uncertain

0.096

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.52

MetaRNN

Uncertain

0.65

MetaSVM

Pathogenic

0.83

MutationAssessor

Uncertain

2.1

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-5.4

REVEL

Uncertain

0.63

Sift

Uncertain

0.012

Sift4G

Uncertain

0.021

Polyphen

0.99

Vest4

0.48

MutPred

0.31

Gain of glycosylation at G214 (P = 0.0189);

MVP

0.87

ClinPred

0.98

GERP RS

4.8

Varity_R

0.69

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over