rs140792905

chr22-30949835-A-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001303256.3(MORC2):c.234T>G(p.Ala78=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00417 in 1,614,092 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (97 hom.)
• Consequence: MORC2 NM_001303256.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.598

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 22-30949835-A-C is Benign according to our data. Variant chr22-30949835-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 475598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-30949835-A-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.598 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00574 (875/152320) while in subpopulation AMR AF= 0.0192 (294/15304). AF 95% confidence interval is 0.0174. There are 10 homozygotes in gnomad4. There are 564 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 874 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MORC2	NM_001303256.3	c.234T>G	p.Ala78=	synonymous_variant	5/26	ENST00000397641.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MORC2	ENST00000397641.8	c.234T>G	p.Ala78=	synonymous_variant	5/26	5	NM_001303256.3	P1
MORC2	ENST00000215862.8	c.48T>G	p.Ala16=	synonymous_variant	6/27	1
MORC2	ENST00000476152.2	n.356T>G		non_coding_transcript_exon_variant	4/7	5

Frequencies

GnomAD3 genomes AF: 0.00574 AC: 874 AN: 152202 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00201

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.0112 AC: 2802 AN: 251250 Hom.: 67 AF XY: 0.00934 AC XY: 1268 AN XY: 135808

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.0489

Gnomad ASJ exome AF: 0.00476

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000555

Gnomad FIN exome AF: 0.0332

Gnomad NFE exome AF: 0.00233

Gnomad OTH exome AF: 0.00865

GnomAD4 exome AF: 0.00401 AC: 5858 AN: 1461772 Hom.: 97 Cov.: 31 AF XY: 0.00375 AC XY: 2725 AN XY: 727198

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.0454

Gnomad4 ASJ exome AF: 0.00478

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000614

Gnomad4 FIN exome AF: 0.0327

Gnomad4 NFE exome AF: 0.00152

Gnomad4 OTH exome AF: 0.00338

GnomAD4 genome AF: 0.00574 AC: 875 AN: 152320 Hom.: 10 Cov.: 32 AF XY: 0.00757 AC XY: 564 AN XY: 74488

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.0192

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.00201

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00338 Hom.: 2

Bravo AF: 0.00563

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.00166

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Charcot-Marie-Tooth disease axonal type 2Z Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Mar 15, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 11, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 16, 2020	- -

Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	8.9
Dann	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs140792905; hg19: chr22-31345821;