2-62858451-A-C

Variant names:

• chr2-62858451-A-C
• rs767340425
• ENST00000263991.9:c.680A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015252.5(EHBP1):​c.680A>C​(p.Gln227Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q227L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EHBP1 NM_015252.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48
• 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]

ENSG00000226605 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09644377).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015252.5. 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.635-718A>C		intron	N/A	NP_001136088.1	Q8NDI1-3
	EHBP1	NM_001354212.1		c.680A>C	p.Gln227Pro	missense	Exon 8 of 25	NP_001341141.1	Q8NDI1-1
	EHBP1	NM_001354213.1		c.680A>C	p.Gln227Pro	missense	Exon 8 of 25	NP_001341142.1	Q8NDI1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHBP1	ENST00000263991.9	TSL:1	c.680A>C	p.Gln227Pro	missense	Exon 8 of 25	ENSP00000263991.5	Q8NDI1-1
	EHBP1	ENST00000431489.6	TSL:1 MANE Select	c.635-718A>C		intron	N/A	ENSP00000403783.1	Q8NDI1-3
	EHBP1	ENST00000405289.5	TSL:1	c.635-718A>C		intron	N/A	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.068
Eigen_PC	Benign	0.093
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.14
Sift	Benign	0.23	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.34
MutPred		0.12		Loss of methylation at K232 (P = 0.1125)
MVP		0.36
MPC		0.12
ClinPred		0.49	T
GERP RS		5.0
Varity_R		0.17
gMVP		0.28
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

dbSNP: rs767340425; hg19: chr2-63085586;