chr1-207899825-G-C

Position:

• chr1-207899825-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001025109.2(CD34):​c.258C>G​(p.Ile86Met) 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. 13/20 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: 3.46

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21150625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD34	NM_001025109.2	c.258C>G	p.Ile86Met	missense_variant	2/8	ENST00000310833.12
CD34	NM_001773.3	c.258C>G	p.Ile86Met	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD34	ENST00000310833.12	c.258C>G	p.Ile86Met	missense_variant	2/8	1	NM_001025109.2	P1
CD34	ENST00000356522.4	c.258C>G	p.Ile86Met	missense_variant	2/8	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 27, 2022

The c.258C>G (p.I86M) alteration is located in exon 2 (coding exon 2) of the CD34 gene. This alteration results from a C to G substitution at nucleotide position 258, causing the isoleucine (I) at amino acid position 86 to be replaced by a methionine (M). 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	0.077
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;.
Eigen	Benign	-0.025
Eigen_PC	Benign	-0.040
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.47	T;T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	1.0	A;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.050
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.076	T;T
Polyphen		0.72	P;P
Vest4		0.22
MutPred		0.27		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.53
MPC		0.73
ClinPred		0.85	D
GERP RS		3.3
Varity_R		0.13
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-208073170;