20-46367811-A-G

Variant names:

• chr20-46367811-A-G
• rs2297056
• NM_133171.5:c.1963-251T>C

Variant summary

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

The NM_133171.5(ELMO2):​c.1963-251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,126 control chromosomes in the GnomAD database, including 2,220 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 0.14 (2220 hom., cov: 31)
• Consequence: ELMO2 NM_133171.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 8 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), G2P, Orphanet
• Ramon syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000273828 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMO2	NM_133171.5	c.1963-251T>C		intron_variant	Intron 21 of 21	ENST00000290246.11	NP_573403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELMO2	ENST00000290246.11	c.1963-251T>C		intron_variant	Intron 21 of 21	1	NM_133171.5	ENSP00000290246.6
ELMO2	ENST00000372176.5	c.1699-251T>C		intron_variant	Intron 21 of 21	5		ENSP00000361249.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20709 AN: 152008 Hom.: 2211 Cov.: 31

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0927

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0907

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.128

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20749 AN: 152126 Hom.: 2220 Cov.: 31 AF XY: 0.132 AC XY: 9813 AN XY: 74366

African (AFR) AF: 0.298 AC: 12356 AN: 41436

American (AMR) AF: 0.0925 AC: 1415 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3470

East Asian (EAS) AF: 0.187 AC: 964 AN: 5166

South Asian (SAS) AF: 0.0912 AC: 440 AN: 4826

European-Finnish (FIN) AF: 0.0387 AC: 411 AN: 10610

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0686 AC: 4664 AN: 68012

Other (OTH) AF: 0.127 AC: 269 AN: 2112

Alfa AF: 0.0910 Hom.: 4132

Bravo AF: 0.148

Asia WGS AF: 0.145 AC: 503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.28
PhyloP100		-0.46
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: rs2297056; hg19: chr20-44996450;