chr22-30932942-C-G

Position:

• chr22-30932942-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001303256.3(MORC2):​c.2469G>C​(p.Arg823Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00733 in 1,614,190 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0076 (79 hom.)
• Consequence: MORC2 NM_001303256.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.289

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 22-30932942-C-G is Benign according to our data. Variant chr22-30932942-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 475582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-30932942-C-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.289 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00482 (734/152310) while in subpopulation SAS AF= 0.0139 (67/4832). AF 95% confidence interval is 0.0112. There are 1 homozygotes in gnomad4. There are 360 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 734 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MORC2	NM_001303256.3	c.2469G>C	p.Arg823Arg	synonymous_variant	22/26	ENST00000397641.8	NP_001290185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MORC2	ENST00000397641.8	c.2469G>C	p.Arg823Arg	synonymous_variant	22/26	5	NM_001303256.3	ENSP00000380763.2

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 733 AN: 152192 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0136

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00760

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00686 AC: 1725 AN: 251462 Hom.: 18 AF XY: 0.00735 AC XY: 999 AN XY: 135902

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00359

Gnomad ASJ exome AF: 0.00496

Gnomad EAS exome AF: 0.000924

Gnomad SAS exome AF: 0.0151

Gnomad FIN exome AF: 0.00291

Gnomad NFE exome AF: 0.00834

Gnomad OTH exome AF: 0.00652

GnomAD4 exome AF: 0.00759 AC: 11100 AN: 1461880 Hom.: 79 Cov.: 31 AF XY: 0.00790 AC XY: 5747 AN XY: 727246

Gnomad4 AFR exome AF: 0.00114

Gnomad4 AMR exome AF: 0.00367

Gnomad4 ASJ exome AF: 0.00490

Gnomad4 EAS exome AF: 0.000756

Gnomad4 SAS exome AF: 0.0147

Gnomad4 FIN exome AF: 0.00303

Gnomad4 NFE exome AF: 0.00790

Gnomad4 OTH exome AF: 0.00679

GnomAD4 genome AF: 0.00482 AC: 734 AN: 152310 Hom.: 1 Cov.: 33 AF XY: 0.00483 AC XY: 360 AN XY: 74480

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.00760

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00647 Hom.: 1

Bravo AF: 0.00458

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.00758

EpiControl AF: 0.00800

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 09, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	MORC2: BP4, BP7, BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 24, 2021	- -

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Mar 15, 2022	- -

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	-0.37
CADD	Benign	6.6
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: rs41279971; hg19: chr22-31328929;