2-176190075-C-T

Position:

• chr2-176190075-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024501.3(HOXD1):​c.920C>T​(p.Ser307Phe) 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)
• Consequence: HOXD1 NM_024501.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.25

Genes affected

HOXD1 (HGNC:5132): (homeobox D1) This gene is a member of the Antp homeobox family and encodes a protein with a homeobox DNA-binding domain. This nuclear protein functions as a sequence-specific transcription factor that is involved in differentiation and limb development. Mutations in this gene have been associated with severe developmental defects on the anterior-posterior (a-p) limb axis. [provided by RefSeq, Jul 2008]

ENSG00000279160 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41788605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXD1	NM_024501.3	c.920C>T	p.Ser307Phe	missense_variant	2/2	ENST00000331462.6	NP_078777.1
HOXD1	XM_047444086.1	c.*240C>T		3_prime_UTR_variant	3/3		XP_047300042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXD1	ENST00000331462.6	c.920C>T	p.Ser307Phe	missense_variant	2/2	1	NM_024501.3	ENSP00000328598.4
ENSG00000279160	ENST00000623777.1	n.2464G>A		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Jan 16, 2024

The c.920C>T (p.S307F) alteration is located in exon 2 (coding exon 2) of the HOXD1 gene. This alteration results from a C to T substitution at nucleotide position 920, causing the serine (S) at amino acid position 307 to be replaced by a phenylalanine (F). 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	Benign	0.13
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.42	T
MetaSVM	Uncertain	0.66	D
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.19
MutPred		0.24		Loss of glycosylation at S307 (P = 0.0025);
MVP		0.94
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.31
gMVP		0.45

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: chr2-177054803; COSMIC: COSV58924422; COSMIC: COSV58924422;