22-30927913-G-C

Position:

• chr22-30927913-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001303256.3(MORC2):​c.3030+106C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,373,480 control chromosomes in the GnomAD database, including 81,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (12131 hom., cov: 33)
  • Exomes 𝑓: 0.33 (69010 hom.)
• Consequence: MORC2 NM_001303256.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.904

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=-0.84).
• BP6: Variant 22-30927913-G-C is Benign according to our data. Variant chr22-30927913-G-C is described in ClinVar as [Benign]. Clinvar id is 1245669.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MORC2	NM_001303256.3	c.3030+106C>G		intron_variant		ENST00000397641.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MORC2	ENST00000397641.8	c.3030+106C>G		intron_variant		5	NM_001303256.3	P1
MORC2-AS1	ENST00000441558.1	n.68-1964G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58482 AN: 152036 Hom.: 12114 Cov.: 33

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.364

GnomAD4 exome AF: 0.329 AC: 401633 AN: 1221324 Hom.: 69010 AF XY: 0.326 AC XY: 198805 AN XY: 609196

Gnomad4 AFR exome AF: 0.523

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.347

GnomAD4 genome AF: 0.385 AC: 58540 AN: 152156 Hom.: 12131 Cov.: 33 AF XY: 0.384 AC XY: 28591 AN XY: 74384

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.360

Alfa AF: 0.355 Hom.: 1221

Bravo AF: 0.393

Asia WGS AF: 0.462 AC: 1606 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.60

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: rs5753394; hg19: chr22-31323900;