2-85356880-C-CAA

Position:

• chr2-85356880-C-CAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001135022.2(ELMOD3):​c.-232-73_-232-72dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0318 in 139,854 control chromosomes in the GnomAD database, including 168 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (168 hom., cov: 32)
  • Exomes 𝑓: 0.0062 (0 hom.)
• Consequence: ELMOD3 NM_001135022.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.706

Genes affected

ELMOD3 (HGNC:26158): (ELMO domain containing 3) This gene encodes a member of the engulfment and cell motility family of GTPase-activating proteins that regulate Arf GTPase proteins. Members of this family are defined by a conserved engulfment and cell motility domain. In rat cochlea, the encoded protein is found in stereocilia, kinocilia and cuticular plate of developing hair cells suggesting a function for this protein in cochlear sensory cells. An allelic variant of this family has been associated with autosomal recessive nonsyndromic deafness-88 in humans. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-85356880-C-CAA is Benign according to our data. Variant chr2-85356880-C-CAA is described in ClinVar as [Benign]. Clinvar id is 1262264.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELMOD3	NM_001135022.2	c.-232-73_-232-72dup		intron_variant		ENST00000409013.8	NP_001128494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELMOD3	ENST00000409013.8	c.-232-73_-232-72dup		intron_variant		1	NM_001135022.2	ENSP00000387139	P1

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 4342 AN: 125056 Hom.: 167 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0315

Gnomad ASJ AF: 0.00359

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00267

Gnomad MID AF: 0.00388

Gnomad NFE AF: 0.000629

Gnomad OTH AF: 0.0225

GnomAD4 exome AF: 0.00616 AC: 91 AN: 14780 Hom.: 0 Cov.: 0 AF XY: 0.00536 AC XY: 41 AN XY: 7650

Gnomad4 AFR exome AF: 0.0466

Gnomad4 AMR exome AF: 0.0165

Gnomad4 ASJ exome AF: 0.00157

Gnomad4 EAS exome AF: 0.0173

Gnomad4 SAS exome AF: 0.00275

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00330

Gnomad4 OTH exome AF: 0.00913

GnomAD4 genome AF: 0.0348 AC: 4350 AN: 125074 Hom.: 168 Cov.: 32 AF XY: 0.0347 AC XY: 2085 AN XY: 60018

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0315

Gnomad4 ASJ AF: 0.00359

Gnomad4 EAS AF: 0.0688

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00267

Gnomad4 NFE AF: 0.000630

Gnomad4 OTH AF: 0.0223

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

Oct 22, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs759699457; hg19: chr2-85584003;