2-17816823-CC-AT

Variant names:

• chr2-17816823-CC-AT
• NM_001105569.3:c.305_306delCCinsAT
• MSGN1 p.Pro102His

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001105569.3(MSGN1):​c.305_306delCCinsAT​(p.Pro102His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: MSGN1 NM_001105569.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 0 publications found

Genes affected

MSGN1 (HGNC:14907): (mesogenin 1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in mesoderm formation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within segment specification and somitogenesis. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MSGN1 Gene-Disease associations (from GenCC):

• skeletal dysplasia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000297720 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105569.3. 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
	MSGN1	NM_001105569.3	MANE Select	c.305_306delCCinsAT	p.Pro102His	missense	N/A	NP_001099039.1	A6NI15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSGN1	ENST00000281047.4	TSL:6 MANE Select	c.305_306delCCinsAT	p.Pro102His	missense	N/A	ENSP00000281047.3	A6NI15
	ENSG00000297720	ENST00000750479.1		n.454-11870_454-11869delGGinsAT		intron	N/A
	ENSG00000297720	ENST00000750480.1		n.416-8091_416-8090delGGinsAT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-17998090;