22-30926746-C-A

Variant names:

• chr22-30926746-C-A
• rs113471863
• NM_001303256.3:c.*57G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.603
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 1197030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 692 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303256.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORC2	NM_001303256.3	MANE Select	c.*57G>T		3_prime_UTR	Exon 26 of 26	NP_001290185.1	Q9Y6X9-1
	MORC2	NM_001303257.2		c.*57G>T		3_prime_UTR	Exon 26 of 26	NP_001290186.1	Q9Y6X9
	MORC2	NM_014941.3		c.*57G>T		3_prime_UTR	Exon 27 of 27	NP_055756.1	Q9Y6X9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORC2	ENST00000397641.8	TSL:5 MANE Select	c.*57G>T		3_prime_UTR	Exon 26 of 26	ENSP00000380763.2	Q9Y6X9-1
	MORC2	ENST00000215862.8	TSL:1	c.*57G>T		3_prime_UTR	Exon 27 of 27	ENSP00000215862.4	Q9Y6X9-2
	MORC2	ENST00000924805.1		c.*57G>T		3_prime_UTR	Exon 26 of 26	ENSP00000594864.1

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

African (AFR) AF: 0.000817 AC: 25 AN: 30606

American (AMR) AF: 0.00169 AC: 72 AN: 42646

Ashkenazi Jewish (ASJ) AF: 0.0000408 AC: 1 AN: 24536

East Asian (EAS) AF: 0.00 AC: 0 AN: 38556

South Asian (SAS) AF: 0.00117 AC: 96 AN: 81908

European-Finnish (FIN) AF: 0.0183 AC: 908 AN: 49510

Middle Eastern (MID) AF: 0.00554 AC: 29 AN: 5238

European-Non Finnish (NFE) AF: 0.00465 AC: 4642 AN: 998046

Other (OTH) AF: 0.00400 AC: 224 AN: 55942

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

African (AFR) AF: 0.000916 AC: 38 AN: 41504

American (AMR) AF: 0.00314 AC: 48 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.0224 AC: 237 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00505 AC: 343 AN: 67980

Other (OTH) AF: 0.00474 AC: 10 AN: 2108

Alfa AF: 0.00181 Hom.: 0

Bravo AF: 0.00353

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.7
DANN	Benign	0.62
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs113471863; hg19: chr22-31322733;