21-32453407-C-G

Position:

• chr21-32453407-C-G

Variant summary

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

The NM_058187.5(EVA1C):​c.256C>G​(p.Gln86Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EVA1C NM_058187.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.37

Genes affected

EVA1C (HGNC:13239): (eva-1 homolog C) Enables heparin binding activity. Colocalizes with extracellular region. [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
EVA1C	NM_058187.5	c.256C>G	p.Gln86Glu	missense_variant	2/8	ENST00000300255.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVA1C	ENST00000300255.7	c.256C>G	p.Gln86Glu	missense_variant	2/8	1	NM_058187.5	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jul 14, 2021

The c.256C>G (p.Q86E) alteration is located in exon 2 (coding exon 2) of the EVA1C gene. This alteration results from a C to G substitution at nucleotide position 256, causing the glutamine (Q) at amino acid position 86 to be replaced by a glutamic acid (E). 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	Benign	0.13
BayesDel_addAF	Benign	0.0051	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0074	T;T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.036	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.65
MutPred		0.44		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.29
MPC		1.0
ClinPred		0.89	D
GERP RS		4.8
Varity_R		0.40
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr21-33825715;