chr5-174724708-G-T

Variant names:

• chr5-174724708-G-T
• rs754789827
• NM_002449.5:c.49G>T

Variant summary

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

The NM_002449.5(MSX2):​c.49G>T​(p.Gly17Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSX2 NM_002449.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.819

Genes affected

MSX2 (HGNC:7392): (msh homeobox 2) This gene encodes a member of the muscle segment homeobox gene family. The encoded protein is a transcriptional repressor whose normal activity may establish a balance between survival and apoptosis of neural crest-derived cells required for proper craniofacial morphogenesis. The encoded protein may also have a role in promoting cell growth under certain conditions and may be an important target for the RAS signaling pathways. Mutations in this gene are associated with parietal foramina 1 and craniosynostosis type 2. [provided by RefSeq, Jul 2008]

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=0.3722459).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSX2	NM_002449.5	c.49G>T	p.Gly17Cys	missense_variant	Exon 1 of 2	ENST00000239243.7	NP_002440.2
MSX2	NM_001363626.2	c.49G>T	p.Gly17Cys	missense_variant	Exon 1 of 2		NP_001350555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSX2	ENST00000239243.7	c.49G>T	p.Gly17Cys	missense_variant	Exon 1 of 2	1	NM_002449.5	ENSP00000239243.5
MSX2	ENST00000507785.2	c.49G>T	p.Gly17Cys	missense_variant	Exon 1 of 2	2		ENSP00000427425.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1439058 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 714274

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.69	T;T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Uncertain	0.36	D
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.5	N;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.019	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.98	D;.
Vest4		0.21
MutPred		0.18		Loss of catalytic residue at G17 (P = 0.0905);Loss of catalytic residue at G17 (P = 0.0905);
MVP		0.97
MPC		0.73
ClinPred		0.87	D
GERP RS		4.4
Varity_R		0.20
gMVP		0.62

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

LitVar

Other links and lift over

dbSNP: rs754789827; hg19: chr5-174151711;