Variant 5-174724762-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002449.5(MSX2):c.103G>C(p.Ala35Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,409,478 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

MSX2
NM_002449.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 1.09

Variant links:

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]

MSX2 links:

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ACMG classification

Classification made for transcript

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=0.16744903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSX2	NM_002449.5 linkuse as main transcript	c.103G>C	p.Ala35Pro	missense_variant	1/2	ENST00000239243.7	NP_002440.2
MSX2	NM_001363626.2 linkuse as main transcript	c.103G>C	p.Ala35Pro	missense_variant	1/2		NP_001350555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSX2	ENST00000239243.7 linkuse as main transcript	c.103G>C	p.Ala35Pro	missense_variant	1/2	1	NM_002449.5	ENSP00000239243	P1
MSX2	ENST00000507785.2 linkuse as main transcript	c.103G>C	p.Ala35Pro	missense_variant	1/2	2		ENSP00000427425

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000631

AC:

AN:

158566

Hom.:

AF XY:

0.0000116

AC XY:

AN XY:

86342

show subpopulations

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:

0.00

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.00000284

AC:

AN:

1409478

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

696452

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000543

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:

0.00000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MSX2-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 12, 2024

The MSX2 c.103G>C variant is predicted to result in the amino acid substitution p.Ala35Pro. To our knowledge, this variant has not been reported in the literature. This variant has been reported once, as a heterozygous allele, in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

AiLife Diagnostics, AiLife Diagnostics

Jul 08, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.70

T;T

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.081

Sift

Benign

0.33

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.0020

B;.

Vest4

0.18

MutPred

0.25

Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);

MVP

0.92

MPC

0.84

ClinPred

0.093

GERP RS

2.2

Varity_R

0.12

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over