1-207899161-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001025109.2(CD34):​c.328G>C​(p.Val110Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CD34
NM_001025109.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.148
Variant links:
Genes affected
CD34 (HGNC:1662): (CD34 molecule) The protein encoded by this gene may play a role in the attachment of stem cells to the bone marrow extracellular matrix or to stromal cells. This single-pass membrane protein is highly glycosylated and phosphorylated by protein kinase C. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.055515885).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD34NM_001025109.2 linkc.328G>C p.Val110Leu missense_variant Exon 3 of 8 ENST00000310833.12 NP_001020280.1 P28906-1
CD34NM_001773.3 linkc.328G>C p.Val110Leu missense_variant Exon 3 of 8 NP_001764.1 P28906-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD34ENST00000310833.12 linkc.328G>C p.Val110Leu missense_variant Exon 3 of 8 1 NM_001025109.2 ENSP00000310036.7 P28906-1
CD34ENST00000356522.4 linkc.328G>C p.Val110Leu missense_variant Exon 3 of 8 1 ENSP00000348916.4 P28906-2
CD34ENST00000485761.1 linkn.-27G>C upstream_gene_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 05, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.328G>C (p.V110L) alteration is located in exon 3 (coding exon 3) of the CD34 gene. This alteration results from a G to C substitution at nucleotide position 328, causing the valine (V) at amino acid position 110 to be replaced by a leucine (L). 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
0.11
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
7.1
DANN
Benign
0.96
DEOGEN2
Benign
0.28
T;.
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.59
T;T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.056
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L;L
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.5
N;N
REVEL
Benign
0.041
Sift
Benign
0.15
T;T
Sift4G
Benign
0.20
T;T
Polyphen
0.13
B;B
Vest4
0.16
MutPred
0.24
Loss of catalytic residue at V110 (P = 0.0055);Loss of catalytic residue at V110 (P = 0.0055);
MVP
0.35
MPC
0.18
ClinPred
0.10
T
GERP RS
0.27
Varity_R
0.078
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: chr1-208072506; API