chr2-62771387-G-C

Variant names:

• chr2-62771387-G-C
• NM_001142616.3:c.307G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001142616.3(EHBP1):​c.307G>C​(p.Glu103Gln) 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: 31)
• Consequence: EHBP1 NM_001142616.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.33
• Publications: 0 publications found

Genes affected

EHBP1 (HGNC:29144): (EH domain binding protein 1) This gene encodes an Eps15 homology domain binding protein. The encoded protein may play a role in endocytic trafficking. A single nucleotide polymorphism in this gene is associated with an aggressive form of prostate cancer. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142616.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHBP1	NM_001142616.3	MANE Select	c.307G>C	p.Glu103Gln	missense	Exon 5 of 23	NP_001136088.1	Q8NDI1-3
	EHBP1	NM_001354212.1		c.307G>C	p.Glu103Gln	missense	Exon 5 of 25	NP_001341141.1	Q8NDI1-1
	EHBP1	NM_001354213.1		c.307G>C	p.Glu103Gln	missense	Exon 5 of 25	NP_001341142.1	Q8NDI1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHBP1	ENST00000431489.6	TSL:1 MANE Select	c.307G>C	p.Glu103Gln	missense	Exon 5 of 23	ENSP00000403783.1	Q8NDI1-3
	EHBP1	ENST00000263991.9	TSL:1	c.307G>C	p.Glu103Gln	missense	Exon 5 of 25	ENSP00000263991.5	Q8NDI1-1
	EHBP1	ENST00000405289.5	TSL:1	c.307G>C	p.Glu103Gln	missense	Exon 4 of 23	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		9.3
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.31		Loss of sheet (P = 0.0315)
MVP		0.48
MPC		0.44
ClinPred		0.98	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.53
Mutation Taster		=35/65	disease causing

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

Other links and lift over

hg19: chr2-62998522;