NM_002449.5:c.-56C>T

Variant names:

• chr5-174724604-C-T
• NM_002449.5:c.-56C>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002449.5(MSX2):​c.-56C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000573 in 1,397,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: MSX2 NM_002449.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.20

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSX2	NM_002449.5	c.-56C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000239243.7	NP_002440.2
MSX2	NM_002449.5	c.-56C>T		5_prime_UTR_variant	Exon 1 of 2	ENST00000239243.7	NP_002440.2
MSX2	NM_001363626.2	c.-56C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2		NP_001350555.1
MSX2	NM_001363626.2	c.-56C>T		5_prime_UTR_variant	Exon 1 of 2		NP_001350555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSX2	ENST00000239243	c.-56C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1	NM_002449.5	ENSP00000239243.5
MSX2	ENST00000239243	c.-56C>T		5_prime_UTR_variant	Exon 1 of 2	1	NM_002449.5	ENSP00000239243.5
MSX2	ENST00000507785	c.-56C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	2		ENSP00000427425.1
MSX2	ENST00000507785	c.-56C>T		5_prime_UTR_variant	Exon 1 of 2	2		ENSP00000427425.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000573 AC: 8 AN: 1397138 Hom.: 0 Cov.: 31 AF XY: 0.00000436 AC XY: 3 AN XY: 688850

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: 0.0000208

Gnomad4 NFE exome AF: 0.00000649

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.3
DANN	Benign	0.95

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-174151607;