rs2240176

Variant names:

• chr22-30925961-G-A
• rs2240176
• ENST00000422995.2:n.1581G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000422995.2(MORC2-AS1):​n.1581G>A variant causes a non coding transcript exon 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-AS1 ENST00000422995.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 16 publications found

Genes affected

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

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease axonal type 2Z

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422995.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORC2	NM_001303256.3	MANE Select	c.*842C>T		3_prime_UTR	Exon 26 of 26	NP_001290185.1
	MORC2-AS1	NR_026920.1		n.1441G>A		non_coding_transcript_exon	Exon 2 of 2
	MORC2	NM_001303257.2		c.*842C>T		3_prime_UTR	Exon 26 of 26	NP_001290186.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORC2-AS1	ENST00000422995.2	TSL:1	n.1581G>A		non_coding_transcript_exon	Exon 3 of 3
	MORC2-AS1	ENST00000432624.3	TSL:1	n.1455G>A		non_coding_transcript_exon	Exon 2 of 2
	MORC2	ENST00000397641.8	TSL:5 MANE Select	c.*842C>T		3_prime_UTR	Exon 26 of 26	ENSP00000380763.2

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

African (AFR) AF: 0.250 AC: 2 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.417 AC: 5 AN: 12

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.272 AC: 93 AN: 342

Middle Eastern (MID) AF: 0.250 AC: 2 AN: 8

European-Non Finnish (NFE) AF: 0.350 AC: 96 AN: 274

Other (OTH) AF: 0.125 AC: 2 AN: 16

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

African (AFR) AF: 0.132 AC: 5455 AN: 41474

American (AMR) AF: 0.284 AC: 4343 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 866 AN: 3468

East Asian (EAS) AF: 0.495 AC: 2527 AN: 5110

South Asian (SAS) AF: 0.213 AC: 1028 AN: 4822

European-Finnish (FIN) AF: 0.271 AC: 2865 AN: 10570

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18873 AN: 67956

Other (OTH) AF: 0.252 AC: 532 AN: 2108

Alfa AF: 0.261 Hom.: 7107

Bravo AF: 0.239

Asia WGS AF: 0.347 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.1
DANN	Benign	0.65
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2240176; hg19: chr22-31321948;