22-30949811-C-T

Variant names:

• chr22-30949811-C-T
• rs150980372
• NM_001303256.3:c.258G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001303256.3(MORC2):​c.258G>A​(p.Lys86Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,850 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: 0.0000021 (0 hom.)
• Consequence: MORC2 NM_001303256.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP7: Synonymous conserved (PhyloP=1.88 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MORC2	NM_001303256.3	c.258G>A	p.Lys86Lys	synonymous_variant	Exon 5 of 26	ENST00000397641.8	NP_001290185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MORC2	ENST00000397641.8	c.258G>A	p.Lys86Lys	synonymous_variant	Exon 5 of 26	5	NM_001303256.3	ENSP00000380763.2
MORC2	ENST00000215862.8	c.72G>A	p.Lys24Lys	synonymous_variant	Exon 6 of 27	1		ENSP00000215862.4
MORC2	ENST00000476152.2	n.380G>A		non_coding_transcript_exon_variant	Exon 4 of 7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	9.0
DANN	Benign	0.86
PhyloP100		1.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs150980372; hg19: chr22-31345797;