chr2-176152072-G-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_014621.3(HOXD4):c.433+6G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000784 in 1,612,796 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0045 ( 3 hom., cov: 31)
Exomes 𝑓: 0.00040 ( 4 hom. )
Consequence
HOXD4
NM_014621.3 splice_donor_region, intron
NM_014621.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00001904
2
Clinical Significance
Conservation
PhyloP100: 2.46
Genes affected
HOXD4 (HGNC:5138): (homeobox D4) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located at 2q31-2q37 chromosome regions. Deletions that removed the entire HOXD gene cluster or 5' end of this cluster have been associated with severe limb and genital abnormalities. The protein encoded by this gene may play a role in determining positional values in developing limb buds. Alternatively spliced variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]
HOXD3 (HGNC:5137): (homeobox D3) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located at 2q31-2q37 chromosome regions. Deletions that removed the entire HOXD gene cluster or 5' end of this cluster have been associated with severe limb and genital abnormalities. The protein encoded by this gene may play a role in the regulation of cell adhesion processes. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 2-176152072-G-T is Benign according to our data. Variant chr2-176152072-G-T is described in ClinVar as [Benign]. Clinvar id is 791157.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 678 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOXD4 | NM_014621.3 | c.433+6G>T | splice_donor_region_variant, intron_variant | ENST00000306324.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOXD4 | ENST00000306324.4 | c.433+6G>T | splice_donor_region_variant, intron_variant | 1 | NM_014621.3 | P1 | |||
HOXD3 | ENST00000432796.2 | c.-85+15073G>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00445 AC: 678AN: 152194Hom.: 3 Cov.: 31
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GnomAD3 exomes AF: 0.00108 AC: 262AN: 241896Hom.: 1 AF XY: 0.000832 AC XY: 110AN XY: 132148
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GnomAD4 exome AF: 0.000401 AC: 586AN: 1460492Hom.: 4 Cov.: 32 AF XY: 0.000332 AC XY: 241AN XY: 726582
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GnomAD4 genome ? AF: 0.00446 AC: 679AN: 152304Hom.: 3 Cov.: 31 AF XY: 0.00455 AC XY: 339AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 29, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at