Variant chr1-207889189-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001025109.2(CD34):c.779T>G(p.Met260Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,458,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CD34
NM_001025109.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.889

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD34	NM_001025109.2 linkuse as main transcript	c.779T>G	p.Met260Arg	missense_variant	6/8	ENST00000310833.12
CD34	NM_001773.3 linkuse as main transcript	c.779T>G	p.Met260Arg	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD34	ENST00000310833.12 linkuse as main transcript	c.779T>G	p.Met260Arg	missense_variant	6/8	1	NM_001025109.2	P1	P28906-1
CD34	ENST00000356522.4 linkuse as main transcript	c.779T>G	p.Met260Arg	missense_variant	6/8	1			P28906-2
CD34	ENST00000367036.7 linkuse as main transcript	c.305T>G	p.Met102Arg	missense_variant	3/5	1
CD34	ENST00000485761.1 linkuse as main transcript	n.425T>G		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251060

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458364

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725764

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:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 07, 2023

The c.779T>G (p.M260R) alteration is located in exon 6 (coding exon 6) of the CD34 gene. This alteration results from a T to G substitution at nucleotide position 779, causing the methionine (M) at amino acid position 260 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

Pathogenic

0.85

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Benign

0.30

T;.;.

Eigen

Benign

0.18

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.0046

MetaRNN

Pathogenic

0.89

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Benign

0.23

Sift

Benign

0.092

T;T;T

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.92

P;P;D

Vest4

0.58

MutPred

0.75

Loss of ubiquitination at K256 (P = 0.0256);.;Loss of ubiquitination at K256 (P = 0.0256);

MVP

0.63

MPC

0.47

ClinPred

0.62

GERP RS

5.5

Varity_R

0.47

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over