rs2890849

Variant names:

• chr5-174730759-G-C
• rs2890849
• NM_002449.5:c.*1176G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-174730759-G-C
• chr5-174730759-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002449.5(MSX2):​c.*1176G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,444 control chromosomes in the GnomAD database, including 49,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.80 (49754 hom., cov: 32)
  • Exomes 𝑓: 0.83 (151 hom.)
• Consequence: MSX2 NM_002449.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.288
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• craniosynostosis 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• parietal foramina

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• parietal foramina with cleidocranial dysplasia

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• parietal foramina 1

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-174730759-G-C is Benign according to our data. Variant chr5-174730759-G-C is described in ClinVar as Benign. ClinVar VariationId is 352864.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002449.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSX2	NM_002449.5	MANE Select	c.*1176G>C		3_prime_UTR	Exon 2 of 2	NP_002440.2
	MSX2	NM_001363626.2		c.*1604G>C		3_prime_UTR	Exon 2 of 2	NP_001350555.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSX2	ENST00000239243.7	TSL:1 MANE Select	c.*1176G>C		3_prime_UTR	Exon 2 of 2	ENSP00000239243.5

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121852 AN: 151890 Hom.: 49736 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.822

GnomAD4 exome AF: 0.828 AC: 361 AN: 436 Hom.: 151 Cov.: 0 AF XY: 0.840 AC XY: 220 AN XY: 262

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.828 AC: 356 AN: 430

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.802 AC: 121919 AN: 152008 Hom.: 49754 Cov.: 32 AF XY: 0.807 AC XY: 59921 AN XY: 74288

African (AFR) AF: 0.632 AC: 26153 AN: 41362

American (AMR) AF: 0.865 AC: 13226 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2910 AN: 3470

East Asian (EAS) AF: 0.985 AC: 5104 AN: 5184

South Asian (SAS) AF: 0.937 AC: 4519 AN: 4824

European-Finnish (FIN) AF: 0.846 AC: 8931 AN: 10560

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58382 AN: 68012

Other (OTH) AF: 0.816 AC: 1712 AN: 2098

Alfa AF: 0.789 Hom.: 2877

Bravo AF: 0.795

Asia WGS AF: 0.919 AC: 3194 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Craniosynostosis 2 (1)
-	-	1	Parietal foramina 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.83
DANN	Benign	0.57
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2890849; hg19: chr5-174157762;