rs2048152

Positions:

• chr5-174725097-G-A
• chr5-174725097-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.374

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 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	UniProt
MSX2	NM_002449.5	c.379+59G>A		intron_variant		ENST00000239243.7
MSX2	NM_001363626.2	c.*3+30G>A		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122891 AN: 151910 Hom.: 51651 Cov.: 32

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

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.: 41 AF XY: 0.900 AC XY: 642383 AN XY: 713452

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.: 32 AF XY: 0.813 AC XY: 60434 AN XY: 74330

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

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

Other links and lift over

dbSNP: rs2048152; hg19: chr5-174152100;