22-30950414-CAT-TAG

Variant names:

• chr22-30950414-CAT-TAG
• ENST00000215862.8:c.1_3delATGinsCTA
• MORC2 p.Met1?

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PVS1_Supporting

The NM_014941.3(MORC2):​c.1_3delATGinsCTA​(p.Met1?) variant causes a start lost change involving the alteration of a 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.

• Frequency: Genomes: not found (cov: 28)
• Consequence: MORC2 NM_014941.3 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.69
• Publications: 0 publications found

Genes affected

MORC2 (HGNC:23573): (MORC family CW-type zinc finger 2) This gene encodes a member of the Microrchidia (MORC) protein superfamily. The encoded protein is known to regulate the condensation of heterochromatin in response to DNA damage and play a role in repressing transcription. The protein has been found to regulate the activity of ATP citrate lyase via specific interaction with this enzyme in the cytosol of lipogenic breast cancer cells. The protein also plays a role in lipogenesis and adipocyte differentiation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

MORC2 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease axonal type 2Z

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 11 codons. Genomic position: 30950386. Lost 0.011 part of the original CDS.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014941.3. 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
	MORC2	NM_001303256.3	MANE Select	c.187_189delATGinsCTA	p.Met63Leu	missense	N/A	NP_001290185.1	Q9Y6X9-1
	MORC2	NM_014941.3		c.1_3delATGinsCTA	p.Met1?	start_lost	N/A	NP_055756.1	Q9Y6X9-2
	MORC2	NM_001303257.2		c.187_189delATGinsCTA	p.Met63Leu	missense	N/A	NP_001290186.1	Q9Y6X9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORC2	ENST00000215862.8	TSL:1	c.1_3delATGinsCTA	p.Met1?	start_lost	N/A	ENSP00000215862.4	Q9Y6X9-2
	MORC2	ENST00000397641.8	TSL:5 MANE Select	c.187_189delATGinsCTA	p.Met63Leu	missense	N/A	ENSP00000380763.2	Q9Y6X9-1
	MORC2	ENST00000924805.1		c.187_189delATGinsCTA	p.Met63Leu	missense	N/A	ENSP00000594864.1

Frequencies

GnomAD3 genomes Cov.: 28

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

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.7

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: chr22-31346400;