Variant 5-174725097-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002449.5(MSX2):c.379+59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 1,590,150 control chromosomes in the GnomAD database, including 634,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.81 ( 51661 hom., cov: 32)

Exomes 𝑓: 0.90 ( 583103 hom. )

Consequence

MSX2
NM_002449.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.374

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-174725097-G-A is Benign according to our data. Variant chr5-174725097-G-A is described in ClinVar as [Benign]. Clinvar id is 1246644.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSX2	NM_002449.5 linkuse as main transcript	c.379+59G>A		intron_variant		ENST00000239243.7	NP_002440.2
MSX2	NM_001363626.2 linkuse as main transcript	c.*3+30G>A		intron_variant			NP_001350555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSX2	ENST00000239243.7 linkuse as main transcript	c.379+59G>A		intron_variant		1	NM_002449.5	ENSP00000239243	P1
MSX2	ENST00000507785.2 linkuse as main transcript	c.*3+30G>A		intron_variant		2		ENSP00000427425

Frequencies

GnomAD3 genomes

AF:

0.809

AC:

122891

AN:

151910

Hom.:

51651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.808

Gnomad AMR

AF:

0.884

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

0.983

Gnomad SAS

AF:

0.905

Gnomad FIN

AF:

0.914

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.903

Gnomad OTH

AF:

0.835

GnomAD3 exomes

AF:

0.898

AC:

180895

AN:

201546

Hom.:

81923

AF XY:

0.901

AC XY:

99904

AN XY:

110906

show subpopulations

Gnomad AFR exome

AF:

0.557

Gnomad AMR exome

AF:

0.933

Gnomad ASJ exome

AF:

0.914

Gnomad EAS exome

AF:

0.983

Gnomad SAS exome

AF:

0.912

Gnomad FIN exome

AF:

0.916

Gnomad NFE exome

AF:

0.905

Gnomad OTH exome

AF:

0.900

GnomAD4 exome

AF:

0.899

AC:

1292157

AN:

1438122

Hom.:

583103

Cov.:

AF XY:

0.900

AC XY:

642383

AN XY:

713452

show subpopulations

Gnomad4 AFR exome

AF:

0.543

Gnomad4 AMR exome

AF:

0.925

Gnomad4 ASJ exome

AF:

0.912

Gnomad4 EAS exome

AF:

0.976

Gnomad4 SAS exome

AF:

0.912

Gnomad4 FIN exome

AF:

0.912

Gnomad4 NFE exome

AF:

0.904

Gnomad4 OTH exome

AF:

0.888

GnomAD4 genome

AF:

0.809

AC:

122943

AN:

152028

Hom.:

51661

Cov.:

AF XY:

0.813

AC XY:

60434

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.556

Gnomad4 AMR

AF:

0.884

Gnomad4 ASJ

AF:

0.910

Gnomad4 EAS

AF:

0.983

Gnomad4 SAS

AF:

0.905

Gnomad4 FIN

AF:

0.914

Gnomad4 NFE

AF:

0.903

Gnomad4 OTH

AF:

0.829

Alfa

AF:

0.865

Hom.:

10587

Bravo

AF:

0.795

Asia WGS

AF:

0.891

AC:

3100

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.9

DANN

Benign

0.97

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