22-30926746-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001303256.3(MORC2):c.*57G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,479,104 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0045 (31 hom.)
• Consequence: MORC2 NM_001303256.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.603

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)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 22-30926746-C-A is Benign according to our data. Variant chr22-30926746-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1197030.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00455 (692/152116) while in subpopulation NFE AF= 0.00505 (343/67980). AF 95% confidence interval is 0.00461. There are 2 homozygotes in gnomad4. There are 397 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 694 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MORC2	NM_001303256.3	c.*57G>T		3_prime_UTR_variant	26/26	ENST00000397641.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MORC2	ENST00000397641.8	c.*57G>T		3_prime_UTR_variant	26/26	5	NM_001303256.3	P1
MORC2-AS1	ENST00000441558.1	n.68-3131C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00457 AC: 694 AN: 151998 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000918

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00315

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00506

Gnomad OTH AF: 0.00479

GnomAD4 exome AF: 0.00452 AC: 5997 AN: 1326988 Hom.: 31 Cov.: 18 AF XY: 0.00455 AC XY: 3030 AN XY: 666176

Gnomad4 AFR exome AF: 0.000817

Gnomad4 AMR exome AF: 0.00169

Gnomad4 ASJ exome AF: 0.0000408

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00117

Gnomad4 FIN exome AF: 0.0183

Gnomad4 NFE exome AF: 0.00465

Gnomad4 OTH exome AF: 0.00400

GnomAD4 genome AF: 0.00455 AC: 692 AN: 152116 Hom.: 2 Cov.: 31 AF XY: 0.00534 AC XY: 397 AN XY: 74360

Gnomad4 AFR AF: 0.000916

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.0224

Gnomad4 NFE AF: 0.00505

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00181 Hom.: 0

Bravo AF: 0.00353

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.7
Dann	Benign	0.62

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: rs113471863; hg19: chr22-31322733;