1-207887803-C-G

Variant names:

• chr1-207887803-C-G
• NM_001025109.2:c.1093G>C

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.77

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]

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 rank	MANE	Protein	UniProt
CD34	NM_001025109.2	c.1093G>C	p.Gly365Arg	missense_variant	Exon 8 of 8	ENST00000310833.12	NP_001020280.1
CD34	NM_001773.3	c.*301G>C		3_prime_UTR_variant	Exon 8 of 8		NP_001764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD34	ENST00000310833.12	c.1093G>C	p.Gly365Arg	missense_variant	Exon 8 of 8	1	NM_001025109.2	ENSP00000310036.7
CD34	ENST00000367036.7	c.619G>C	p.Gly207Arg	missense_variant	Exon 5 of 5	1		ENSP00000356003.3
CD34	ENST00000356522	c.*301G>C		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000348916.4
CD34	ENST00000485761.1	n.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

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;