2-172100682-T-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_004405.4(DLX2):c.848A>T(p.Tyr283Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000418 in 1,556,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
DLX2
NM_004405.4 missense
NM_004405.4 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 5.90
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.31871307).
BS2
High AC in GnomAdExome4 at 62 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152046Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000110 AC: 20AN: 181234Hom.: 0 AF XY: 0.000140 AC XY: 14AN XY: 100082
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GnomAD4 exome AF: 0.0000442 AC: 62AN: 1403922Hom.: 0 Cov.: 31 AF XY: 0.0000660 AC XY: 46AN XY: 696998
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74388
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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 | Apr 09, 2024 | The c.848A>T (p.Y283F) alteration is located in exon 3 (coding exon 3) of the DLX2 gene. This alteration results from a A to T substitution at nucleotide position 848, causing the tyrosine (Y) at amino acid position 283 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of loop (P = 0.1242);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at