2-85356880-C-CA

Position:

• chr2-85356880-C-CA

Variant summary

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

The NM_001135022.2(ELMOD3):​c.-232-72dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 139,756 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0088 (7 hom., cov: 32)
  • Exomes 𝑓: 0.088 (0 hom.)
• Consequence: ELMOD3 NM_001135022.2 intron
• Clinical Significance: Likely 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-CA is Benign according to our data. Variant chr2-85356880-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 1316699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0863 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00870 AC: 1087 AN: 124920 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00488

Gnomad ASJ AF: 0.000328

Gnomad EAS AF: 0.00226

Gnomad SAS AF: 0.000747

Gnomad FIN AF: 0.00382

Gnomad MID AF: 0.00391

Gnomad NFE AF: 0.00221

Gnomad OTH AF: 0.00593

GnomAD4 exome AF: 0.0881 AC: 1306 AN: 14818 Hom.: 0 Cov.: 0 AF XY: 0.0876 AC XY: 672 AN XY: 7670

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.0602

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.0892

Gnomad4 SAS exome AF: 0.0579

Gnomad4 FIN exome AF: 0.0879

Gnomad4 NFE exome AF: 0.0901

Gnomad4 OTH exome AF: 0.0820

GnomAD4 genome AF: 0.00879 AC: 1098 AN: 124938 Hom.: 7 Cov.: 32 AF XY: 0.00936 AC XY: 561 AN XY: 59938

Gnomad4 AFR AF: 0.0250

Gnomad4 AMR AF: 0.00487

Gnomad4 ASJ AF: 0.000328

Gnomad4 EAS AF: 0.00226

Gnomad4 SAS AF: 0.000751

Gnomad4 FIN AF: 0.00382

Gnomad4 NFE AF: 0.00221

Gnomad4 OTH AF: 0.00706

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs759699457; hg19: chr2-85584003;