1-207899161-C-G

Variant names:

• chr1-207899161-C-G
• NM_001025109.2:c.328G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.148

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 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
CD34	NM_001025109.2	c.328G>C	p.Val110Leu	missense_variant	Exon 3 of 8	ENST00000310833.12	NP_001020280.1
CD34	NM_001773.3	c.328G>C	p.Val110Leu	missense_variant	Exon 3 of 8		NP_001764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD34	ENST00000310833.12	c.328G>C	p.Val110Leu	missense_variant	Exon 3 of 8	1	NM_001025109.2	ENSP00000310036.7
CD34	ENST00000356522.4	c.328G>C	p.Val110Leu	missense_variant	Exon 3 of 8	1		ENSP00000348916.4
CD34	ENST00000485761.1	n.-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

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;