rs2240176

Positions:

• chr22-30925961-G-A
• chr22-30925961-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001303256.3(MORC2):​c.*842C>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 0.242 in 152,664 control chromosomes in the GnomAD database, including 5,099 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (5058 hom., cov: 31)
  • Exomes 𝑓: 0.30 (41 hom.)
• Consequence: MORC2 NM_001303256.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MORC2	NM_001303256.3	c.*842C>T		3_prime_UTR_variant	26/26	ENST00000397641.8	NP_001290185.1
MORC2-AS1	NR_026920.1	n.1441G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MORC2	ENST00000397641.8	c.*842C>T		3_prime_UTR_variant	26/26	5	NM_001303256.3	ENSP00000380763	P1
MORC2-AS1	ENST00000441558.1	n.67+3446G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36758 AN: 151874 Hom.: 5058 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.301 AC: 202 AN: 672 Hom.: 41 Cov.: 0 AF XY: 0.340 AC XY: 144 AN XY: 424

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.242 AC: 36762 AN: 151992 Hom.: 5058 Cov.: 31 AF XY: 0.242 AC XY: 18009 AN XY: 74284

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.252

Alfa AF: 0.268 Hom.: 5661

Bravo AF: 0.239

Asia WGS AF: 0.347 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.1
DANN	Benign	0.65

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: rs2240176; hg19: chr22-31321948;