22-30932942-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. R823R) has been classified 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

Publications

3 publications found

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 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

MORC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 475582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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

GnomAD2 exomes

AF:

0.00686

AC:

1725

AN:

251462

AF XY:

0.00735

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 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

African (AFR)

AF:

0.00114

AC:

AN:

33480

American (AMR)

AF:

0.00367

AC:

164

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

128

AN:

26134

East Asian (EAS)

AF:

0.000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0147

AC:

1266

AN:

86258

European-Finnish (FIN)

AF:

0.00303

AC:

162

AN:

53416

Middle Eastern (MID)

AF:

0.0205

AC:

118

AN:

5768

European-Non Finnish (NFE)

AF:

0.00790

AC:

8784

AN:

1112006

Other (OTH)

AF:

0.00679

AC:

410

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

691

1381

2072

2762

3453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

336

672

1008

1344

1680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00482

AC:

734

AN:

152310

Hom.:

Cov.:

AF XY:

0.00483

AC XY:

360

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

41560

American (AMR)

AF:

0.00248

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5174

South Asian (SAS)

AF:

0.0139

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00273

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00760

AC:

517

AN:

68018

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

118

158

197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

May 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 -

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

- -

Sep 24, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease axonal type 2Z

Benign:2

Mar 15, 2022

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

(source)

DANN

Benign

0.79

PhyloP100

0.29

PromoterAI

-0.0035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over