1-207887803-C-G

Variant summary

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

The NM_001025109.2(CD34):​c.1093G>C​(p.Gly365Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G365D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

CD34
NM_001025109.2 missense

Scores

2
12
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77
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 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 rank MANE Protein UniProt
CD34NM_001025109.2 linkc.1093G>C p.Gly365Arg missense_variant Exon 8 of 8 ENST00000310833.12 NP_001020280.1 P28906-1
CD34NM_001773.3 linkc.*301G>C 3_prime_UTR_variant Exon 8 of 8 NP_001764.1 P28906-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD34ENST00000310833.12 linkc.1093G>C p.Gly365Arg missense_variant Exon 8 of 8 1 NM_001025109.2 ENSP00000310036.7 P28906-1
CD34ENST00000367036.7 linkc.619G>C p.Gly207Arg missense_variant Exon 5 of 5 1 ENSP00000356003.3 Q5JTA5
CD34ENST00000356522 linkc.*301G>C 3_prime_UTR_variant Exon 8 of 8 1 ENSP00000348916.4 P28906-2
CD34ENST00000485761.1 linkn.618+879G>C intron_variant Intron 5 of 5 5

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 25, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1093G>C (p.G365R) alteration is located in exon 8 (coding exon 8) of the CD34 gene. This alteration results from a G to C substitution at nucleotide position 1093, causing the glycine (G) at amino acid position 365 to be replaced by an arginine (R). 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
Uncertain
0.54
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.38
T;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Benign
0.67
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.056
D
MetaRNN
Uncertain
0.57
D;D
MetaSVM
Benign
-0.56
T
MutationAssessor
Uncertain
2.5
M;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-5.1
D;D
REVEL
Uncertain
0.39
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
D;D
Vest4
0.47
MutPred
0.65
Gain of solvent accessibility (P = 0.0016);.;
MVP
0.80
MPC
0.81
ClinPred
1.0
D
GERP RS
4.0
Varity_R
0.57
gMVP
0.30

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: chr1-208061148; API