rs767914603

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001303256.3(MORC2):ā€‹c.2754T>Gā€‹(p.Cys918Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

MORC2
NM_001303256.3 missense

Scores

5
6
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.73
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-AS1 (HGNC:26662): (MORC2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MORC2. . Gene score misZ: 3.2251 (greater than the threshold 3.09). Trascript score misZ: 4.4393 (greater than threshold 3.09). The gene has 25 curated pathogenic missense variants (we use a threshold of 10). The gene has 13 curated benign missense variants. GenCC has associacion of the gene with Leigh syndrome, Charcot-Marie-Tooth disease axonal type 2Z, developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MORC2NM_001303256.3 linkc.2754T>G p.Cys918Trp missense_variant 24/26 ENST00000397641.8 NP_001290185.1 Q9Y6X9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MORC2ENST00000397641.8 linkc.2754T>G p.Cys918Trp missense_variant 24/265 NM_001303256.3 ENSP00000380763.2 Q9Y6X9-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251336
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135834
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461664
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727150
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Benign
-0.092
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.36
T;.
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Benign
0.043
D
MetaRNN
Uncertain
0.67
D;D
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
2.0
M;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-6.5
D;D
REVEL
Benign
0.26
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.017
D;D
Polyphen
1.0
D;.
Vest4
0.69
MutPred
0.69
Gain of MoRF binding (P = 0.0485);.;
MVP
0.26
MPC
2.2
ClinPred
0.99
D
GERP RS
4.9
Varity_R
0.80
gMVP
0.77

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.

Other links and lift over

dbSNP: rs767914603; hg19: chr22-31328433; API