22-30932942-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.289

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
MORC2	NM_001303256.3 link	c.2469G>C	p.Arg823Arg	synonymous_variant	Exon 22 of 26	ENST00000397641.8	NP_001290185.1	Q9Y6X9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MORC2	ENST00000397641.8 link	c.2469G>C	p.Arg823Arg	synonymous_variant	Exon 22 of 26	5	NM_001303256.3	ENSP00000380763.2		Q9Y6X9-1

Frequencies

GnomAD3 genomes

AF:

0.00482

AC:

733

AN:

152192

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00735

AC XY:

999

AN XY:

135902

show subpopulations

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.:

Cov.:

AF XY:

0.00790

AC XY:

5747

AN XY:

727246

show subpopulations

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.:

Cov.:

AF XY:

0.00483

AC XY:

360

AN XY:

74480

show subpopulations

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.:

Bravo

AF:

0.00458

Asia WGS

AF:

0.00520

AC:

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

LINK: link

Submissions by phenotype

not provided

Benign:4

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MORC2: BP4, BP7, BS1, BS2 -

Sep 24, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 09, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Charcot-Marie-Tooth disease axonal type 2Z

Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy

Benign:1

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over