rs4242182

chr5-174729165-T-Achr5-174729165-T-Cchr5-174729165-T-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_002449.5(MSX2):c.386T>A(p.Met129Lys) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M129T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSX2 NM_002449.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.52

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 Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.33040506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSX2	NM_002449.5	c.386T>A	p.Met129Lys	missense_variant	2/2	ENST00000239243.7
MSX2	NM_001363626.2	c.*10T>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSX2	ENST00000239243.7	c.386T>A	p.Met129Lys	missense_variant	2/2	1	NM_002449.5	P1
MSX2	ENST00000507785.2	c.*10T>A		3_prime_UTR_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251302 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135852

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000274 AC: 4 AN: 1461804 Hom.: 0 Cov.: 51 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
Cadd	Benign	23
Dann	Benign	0.95
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.058
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	0.50	D
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	4.3e-31	P;P
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.25
Sift	Benign	0.11	T
Sift4G	Benign	0.43	T
Polyphen		0.011	B
Vest4		0.23
MutPred		0.36		Gain of methylation at M129 (P = 0.009);
MVP		0.98
MPC		0.68
ClinPred		0.25	T
GERP RS		5.3
Varity_R		0.52
gMVP		0.61

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: rs4242182; hg19: chr5-174156168;