20-46367666-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_133171.5(ELMO2):c.1963-106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 843,202 control chromosomes in the GnomAD database, including 9,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1909 hom., cov: 32)
  • Exomes 𝑓: 0.14 (7550 hom.)
• Consequence: ELMO2 NM_133171.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.394

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-46367666-A-G is Benign according to our data. Variant chr20-46367666-A-G is described in ClinVar as [Benign]. Clinvar id is 1245384.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELMO2	NM_133171.5	c.1963-106T>C		intron_variant		ENST00000290246.11
LOC124904917	XR_007067614.1	n.182+2946A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELMO2	ENST00000290246.11	c.1963-106T>C		intron_variant		1	NM_133171.5	P4
	ENST00000651935.1	n.151+2946A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23239 AN: 152104 Hom.: 1908 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0810

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0725

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.139 AC: 96130 AN: 690980 Hom.: 7550 AF XY: 0.139 AC XY: 48685 AN XY: 349762

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.0764

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.0766

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.153 AC: 23258 AN: 152222 Hom.: 1909 Cov.: 32 AF XY: 0.149 AC XY: 11113 AN XY: 74430

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0809

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0725

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.158

Alfa AF: 0.154 Hom.: 438

Bravo AF: 0.163

Asia WGS AF: 0.112 AC: 388 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.3
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs2297057; hg19: chr20-44996305; COSMIC: COSV51686798; COSMIC: COSV51686798;