rs371351399

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001303256.3(MORC2):c.732C>T(p.Ala244Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

MORC2
NM_001303256.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.178

Publications

1 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 22-30941525-G-A is Benign according to our data. Variant chr22-30941525-G-A is described in CliVar as Likely_benign. Clinvar id is 475599.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-30941525-G-A is described in CliVar as Likely_benign. Clinvar id is 475599.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-30941525-G-A is described in CliVar as Likely_benign. Clinvar id is 475599.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-30941525-G-A is described in CliVar as Likely_benign. Clinvar id is 475599.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-30941525-G-A is described in CliVar as Likely_benign. Clinvar id is 475599.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-30941525-G-A is described in CliVar as Likely_benign. Clinvar id is 475599.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-30941525-G-A is described in CliVar as Likely_benign. Clinvar id is 475599.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-30941525-G-A is described in CliVar as Likely_benign. Clinvar id is 475599.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-30941525-G-A is described in CliVar as Likely_benign. Clinvar id is 475599.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-30941525-G-A is described in CliVar as Likely_benign. Clinvar id is 475599.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-30941525-G-A is described in CliVar as Likely_benign. Clinvar id is 475599.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-30941525-G-A is described in CliVar as Likely_benign. Clinvar id is 475599.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.178 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0000394 (6/152216) while in subpopulation NFE AF = 0.0000735 (5/68042). AF 95% confidence interval is 0.0000285. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MORC2	NM_001303256.3 link	c.732C>T	p.Ala244Ala	synonymous_variant	Exon 9 of 26	ENST00000397641.8	NP_001290185.1	Q9Y6X9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MORC2	ENST00000397641.8 link	c.732C>T	p.Ala244Ala	synonymous_variant	Exon 9 of 26	5	NM_001303256.3	ENSP00000380763.2	Q9Y6X9-1
MORC2	ENST00000215862.8 link	c.546C>T	p.Ala182Ala	synonymous_variant	Exon 10 of 27	1		ENSP00000215862.4	Q9Y6X9-2
MORC2	ENST00000469915.1 link	n.286C>T		non_coding_transcript_exon_variant	Exon 3 of 6	3
MORC2	ENST00000675601.1 link	n.574C>T		non_coding_transcript_exon_variant	Exon 5 of 22

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000399

AC:

AN:

250604

AF XY:

0.0000443

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1461706

Hom.:

Cov.:

AF XY:

0.0000756

AC XY:

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53344

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000728

AC:

AN:

1111928

Other (OTH)

AF:

0.0000497

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000394

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000768

Hom.:

Bravo

AF:

0.0000416

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease axonal type 2Z

Benign:1

Sep 10, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

MORC2-related disorder

Benign:1

Mar 05, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.18

Mutation Taster

=87/13

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