20-46369063-C-A

Variant names:

• chr20-46369063-C-A
• rs2297055
• NM_133171.5:c.1885-95G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133171.5(ELMO2):​c.1885-95G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000104 in 964,778 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: ELMO2 NM_133171.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 0 publications found

Genes affected

ELMO2 (HGNC:17233): (engulfment and cell motility 2) The protein encoded by this gene interacts with the dedicator of cyto-kinesis 1 protein. Similarity to a C. elegans protein suggests that this protein may function in phagocytosis of apoptotic cells and in cell migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ELMO2 Gene-Disease associations (from GenCC):

• primary intraosseous venous malformation

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• Ramon syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000273828 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133171.5. 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
	ELMO2	NM_133171.5	MANE Select	c.1885-95G>T		intron	N/A	NP_573403.1	Q96JJ3-1
	ELMO2	NM_182764.3		c.1885-95G>T		intron	N/A	NP_877496.1	Q96JJ3-1
	ELMO2	NM_001318253.2		c.1621-95G>T		intron	N/A	NP_001305182.1	Q96JJ3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMO2	ENST00000290246.11	TSL:1 MANE Select	c.1885-95G>T		intron	N/A	ENSP00000290246.6	Q96JJ3-1
	ELMO2	ENST00000396391.5	TSL:1	c.1885-95G>T		intron	N/A	ENSP00000379673.1	Q96JJ3-1
	ELMO2	ENST00000372176.5	TSL:5	c.1621-95G>T		intron	N/A	ENSP00000361249.1	Q96JJ3-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000104 AC: 1 AN: 964778 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 498430

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23492

American (AMR) AF: 0.00 AC: 0 AN: 41074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21688

East Asian (EAS) AF: 0.00 AC: 0 AN: 36970

South Asian (SAS) AF: 0.00 AC: 0 AN: 73294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3712

European-Non Finnish (NFE) AF: 0.00000149 AC: 1 AN: 670660

Other (OTH) AF: 0.00 AC: 0 AN: 43688

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.94
DANN	Benign	0.79
PhyloP100		-1.2

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: rs2297055; hg19: chr20-44997702;