chr2-172088100-C-T

Variant names:

• chr2-172088100-C-T
• NM_178120.5:c.611C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178120.5(DLX1):​c.611C>T​(p.Ala204Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DLX1 NM_178120.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.27
• Publications: 0 publications found

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]

ENSG00000288958 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2747296).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178120.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX1	NM_178120.5	MANE Select	c.611C>T	p.Ala204Val	missense	Exon 3 of 3	NP_835221.2	X5D2F9
	DLX1	NM_001038493.2		c.*21C>T		3_prime_UTR	Exon 2 of 2	NP_001033582.1	P56177-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX1	ENST00000361725.5	TSL:1 MANE Select	c.611C>T	p.Ala204Val	missense	Exon 3 of 3	ENSP00000354478.4	P56177-1
	DLX1	ENST00000341900.6	TSL:1	c.*21C>T		3_prime_UTR	Exon 2 of 2	ENSP00000341786.6	P56177-2
	DLX1	ENST00000475989.2	TSL:2	n.685C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000207 AC: 3 AN: 1452518 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 722352

African (AFR) AF: 0.00 AC: 0 AN: 32964

American (AMR) AF: 0.00 AC: 0 AN: 43348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25618

East Asian (EAS) AF: 0.00 AC: 0 AN: 39206

South Asian (SAS) AF: 0.00 AC: 0 AN: 85140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1107356

Other (OTH) AF: 0.00 AC: 0 AN: 59978

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	0.97	L
PhyloP100		5.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.023	D
Polyphen		0.31	B
Vest4		0.18
MutPred		0.17		Loss of methylation at R203 (P = 0.1231)
MVP		0.78
MPC		1.5
ClinPred		0.97	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.53
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

hg19: chr2-172952828;