19-45607375-A-C

Variant names:

• chr19-45607375-A-C
• rs141570927
• ENST00000589876.5:c.1956T>G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The ENST00000589876.5(EML2):​c.1956T>G​(p.Ala652Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 398,726 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (1 hom.)
• Consequence: EML2 ENST00000589876.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

Genes affected

EML2 (HGNC:18035): (EMAP like 2) Enables microtubule binding activity. Involved in negative regulation of microtubule polymerization and regulation of microtubule nucleation. Colocalizes with mitotic spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-45607375-A-C is Benign according to our data. Variant chr19-45607375-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2650118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.36 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EML2	ENST00000589876.5	c.1956T>G	p.Ala652Ala	synonymous_variant	Exon 19 of 19	1		ENSP00000464789.1

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 212 AN: 152178 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.000955

GnomAD4 exome AF: 0.00164 AC: 405 AN: 246430 Hom.: 1 Cov.: 0 AF XY: 0.00167 AC XY: 209 AN XY: 124904

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.000269

Gnomad4 ASJ exome AF: 0.000216

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00891

Gnomad4 FIN exome AF: 0.000672

Gnomad4 NFE exome AF: 0.00207

Gnomad4 OTH exome AF: 0.00128

GnomAD4 genome AF: 0.00138 AC: 210 AN: 152296 Hom.: 1 Cov.: 31 AF XY: 0.00130 AC XY: 97 AN XY: 74478

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00663

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00232

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00132 Hom.: 0

Bravo AF: 0.00124

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EML2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs141570927; hg19: chr19-46110633;