Variant chr1-207899829-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_001025109.2(CD34):c.254A>G(p.Asn85Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,330 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CD34
NM_001025109.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.170

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]

CD34 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity CD34_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03588763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD34	NM_001025109.2 linkuse as main transcript	c.254A>G	p.Asn85Ser	missense_variant	2/8	ENST00000310833.12
CD34	NM_001773.3 linkuse as main transcript	c.254A>G	p.Asn85Ser	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD34	ENST00000310833.12 linkuse as main transcript	c.254A>G	p.Asn85Ser	missense_variant	2/8	1	NM_001025109.2	P1	P28906-1
CD34	ENST00000356522.4 linkuse as main transcript	c.254A>G	p.Asn85Ser	missense_variant	2/8	1			P28906-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457330

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.254A>G (p.N85S) alteration is located in exon 2 (coding exon 2) of the CD34 gene. This alteration results from a A to G substitution at nucleotide position 254, causing the asparagine (N) at amino acid position 85 to be replaced by a serine (S). 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

0.066

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.28

DANN

Benign

0.15

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.83

N;N

REVEL

Benign

0.0050

Sift

Benign

0.84

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.0020

B;B

Vest4

0.076

MutPred

0.17

Gain of glycosylation at N85 (P = 0.0405);Gain of glycosylation at N85 (P = 0.0405);

MVP

0.19

MPC

0.15

ClinPred

0.018

GERP RS

-3.4

Varity_R

0.010

gMVP

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over