7-97020792-G-A

Position:

• chr7-97020792-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005221.6(DLX5):​c.814C>T​(p.Pro272Ser) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DLX5 NM_005221.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.81

Genes affected

DLX5 (HGNC:2918): (distal-less homeobox 5) This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. The encoded protein may play a role in bone development and fracture healing. Mutation in this gene, which is located in a tail-to-tail configuration with another member of the family on the long arm of chromosome 7, may be associated with split-hand/split-foot malformation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24157706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX5	NM_005221.6	c.814C>T	p.Pro272Ser	missense_variant	3/3	ENST00000648378.1	NP_005212.1
DLX5	XM_005250185.4	c.430C>T	p.Pro144Ser	missense_variant	3/3		XP_005250242.1
DLX5	XM_017011803.2	c.430C>T	p.Pro144Ser	missense_variant	3/3		XP_016867292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX5	ENST00000648378.1	c.814C>T	p.Pro272Ser	missense_variant	3/3		NM_005221.6	ENSP00000498116	P1
DLX5	ENST00000493764.1	n.936C>T		non_coding_transcript_exon_variant	3/3	5

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 provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 05, 2023

This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 272 of the DLX5 protein (p.Pro272Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DLX5-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.0026	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.029
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	.;T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.95	N;.
REVEL	Uncertain	0.38
Sift	Benign	0.23	T;.
Sift4G	Benign	0.82	T;.
Polyphen		0.0010	B;B
Vest4		0.26
MutPred		0.23		Loss of catalytic residue at P272 (P = 0.0132);Loss of catalytic residue at P272 (P = 0.0132);
MVP		0.53
MPC		0.47
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.12
gMVP		0.53

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: chr7-96650104; COSMIC: COSV56031794; COSMIC: COSV56031794;