chr2-85362912-C-T

Position:

• chr2-85362912-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001135022.2(ELMOD3):​c.130-185C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 152,130 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.038 (152 hom., cov: 32)
• Consequence: ELMOD3 NM_001135022.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.266

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 2-85362912-C-T is Benign according to our data. Variant chr2-85362912-C-T is described in ClinVar as [Benign]. Clinvar id is 1268939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELMOD3	NM_001135022.2	c.130-185C>T		intron_variant		ENST00000409013.8	NP_001128494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELMOD3	ENST00000409013.8	c.130-185C>T		intron_variant		1	NM_001135022.2	ENSP00000387139	P1

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5852 AN: 152012 Hom.: 151 Cov.: 32

Gnomad AFR AF: 0.00996

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0848

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.0459

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

GnomAD4 genome AF: 0.0385 AC: 5850 AN: 152130 Hom.: 152 Cov.: 32 AF XY: 0.0383 AC XY: 2847 AN XY: 74378

Gnomad4 AFR AF: 0.00993

Gnomad4 AMR AF: 0.0390

Gnomad4 ASJ AF: 0.0848

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0332

Gnomad4 FIN AF: 0.0326

Gnomad4 NFE AF: 0.0575

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0460 Hom.: 27

Bravo AF: 0.0372

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.3
DANN	Benign	0.41

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: rs143887529; hg19: chr2-85590035;