chr2-54829367-G-A

Position:

• chr2-54829367-G-A

Variant summary

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

The NM_001039753.4(EML6):​c.737G>A​(p.Cys246Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EML6 NM_001039753.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

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	Protein	UniProt
EML6	NM_001039753.4	c.737G>A	p.Cys246Tyr	missense_variant	7/42	ENST00000356458.8	NP_001034842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EML6	ENST00000356458.8	c.737G>A	p.Cys246Tyr	missense_variant	7/42	5	NM_001039753.4	ENSP00000348842	P1
EML6	ENST00000673912.1	c.737G>A	p.Cys246Tyr	missense_variant, NMD_transcript_variant	7/43			ENSP00000501234

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399508 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 690266

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Oct 17, 2023

The c.737G>A (p.C246Y) alteration is located in exon 6 (coding exon 6) of the EML6 gene. This alteration results from a G to A substitution at nucleotide position 737, causing the cysteine (C) at amino acid position 246 to be replaced by a tyrosine (Y). 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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0078	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.42
Sift	Benign	0.39	T
Sift4G	Benign	0.51	T
Polyphen		0.33	B
Vest4		0.87
MutPred		0.40		Gain of disorder (P = 0.0711);
MVP		0.52
MPC		0.33
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.45
gMVP		0.77

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: chr2-55056504;