2-172088195-A-C

Position:

• chr2-172088195-A-C

Variant summary

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

The NM_178120.5(DLX1):​c.706A>C​(p.Ser236Arg) variant causes a missense change involving the alteration of a non-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: DLX1 NM_178120.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.42

Genes affected

DLX1 (HGNC:2914): (distal-less homeobox 1) This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. The encoded protein is localized to the nucleus where it may function as a transcriptional regulator of signals from multiple TGF-{beta} superfamily members. The encoded protein may play a role in the control of craniofacial patterning and the differentiation and survival of inhibitory neurons in the forebrain. This gene is located in a tail-to-tail configuration with another member of the family on the long arm of chromosome 2. Alternatively spliced transcript variants encoding different isoforms have been described. [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
DLX1	NM_178120.5	c.706A>C	p.Ser236Arg	missense_variant	3/3	ENST00000361725.5	NP_835221.2
DLX1	NM_001038493.2	c.*116A>C		3_prime_UTR_variant	2/2		NP_001033582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX1	ENST00000361725.5	c.706A>C	p.Ser236Arg	missense_variant	3/3	1	NM_178120.5	ENSP00000354478	P1
DLX1	ENST00000341900.6	c.*116A>C		3_prime_UTR_variant	2/2	1		ENSP00000341786
DLX1	ENST00000475989.2	n.780A>C		non_coding_transcript_exon_variant	2/2	2
DLX1	ENST00000550686.1	n.395A>C		non_coding_transcript_exon_variant	2/2	4

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

May 13, 2024

The c.706A>C (p.S236R) alteration is located in exon 3 (coding exon 3) of the DLX1 gene. This alteration results from a A to C substitution at nucleotide position 706, causing the serine (S) at amino acid position 236 to be replaced by an arginine (R). 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	0.92
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.0	N
REVEL	Pathogenic	0.67
Sift	Benign	0.041	D
Sift4G	Benign	0.068	T
Polyphen		0.98	D
Vest4		0.31
MutPred		0.34		Gain of MoRF binding (P = 0.0085);
MVP		0.91
MPC		1.9
ClinPred		0.89	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.85

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: chr2-172952923;