2-54725078-C-T

Position:

• chr2-54725078-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001039753.4(EML6):​c.17C>T​(p.Ala6Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,375,300 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: EML6 NM_001039753.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.42

Genes affected

EML6 (HGNC:35412): (EMAP like 6) Predicted to enable microtubule binding activity. Predicted to be located in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EML6	NM_001039753.4	c.17C>T	p.Ala6Val	missense_variant	2/42	ENST00000356458.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML6	ENST00000356458.8	c.17C>T	p.Ala6Val	missense_variant	2/42	5	NM_001039753.4	P1
EML6	ENST00000673912.1	c.17C>T	p.Ala6Val	missense_variant, NMD_transcript_variant	2/43
EML6	ENST00000491655.1	n.235+408C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000131 AC: 18 AN: 1375300 Hom.: 0 Cov.: 31 AF XY: 0.0000133 AC XY: 9 AN XY: 678438

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000168

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.17C>T (p.A6V) alteration is located in exon 1 (coding exon 1) of the EML6 gene. This alteration results from a C to T substitution at nucleotide position 17, causing the alanine (A) at amino acid position 6 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.20
Sift	Benign	0.32	T
Sift4G	Benign	0.52	T
Polyphen		0.79	P
Vest4		0.59
MutPred		0.40		Gain of MoRF binding (P = 0.0692);
MVP		0.32
MPC		0.27
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.12
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-54952215;