1-207888713-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001025109.2(CD34):​c.941G>A​(p.Arg314His) variant causes a missense change. The variant allele was found at a frequency of 0.0000768 in 1,614,080 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: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

CD34
NM_001025109.2 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.25
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD34NM_001025109.2 linkc.941G>A p.Arg314His missense_variant Exon 7 of 8 ENST00000310833.12 NP_001020280.1 P28906-1
CD34NM_001773.3 linkc.941G>A p.Arg314His missense_variant Exon 7 of 8 NP_001764.1 P28906-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD34ENST00000310833.12 linkc.941G>A p.Arg314His missense_variant Exon 7 of 8 1 NM_001025109.2 ENSP00000310036.7 P28906-1
CD34ENST00000356522.4 linkc.941G>A p.Arg314His missense_variant Exon 7 of 8 1 ENSP00000348916.4 P28906-2
CD34ENST00000367036.7 linkc.467G>A p.Arg156His missense_variant Exon 4 of 5 1 ENSP00000356003.3 Q5JTA5
CD34ENST00000485761.1 linkn.587G>A non_coding_transcript_exon_variant Exon 5 of 6 5

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000123
AC:
31
AN:
251390
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.000397
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000211
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000787
AC:
115
AN:
1461870
Hom.:
0
Cov.:
32
AF XY:
0.0000825
AC XY:
60
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.000230
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000936
Gnomad4 NFE exome
AF:
0.0000827
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152210
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000115
Hom.:
0
Bravo
AF:
0.0000756
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000140
AC:
17
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 29, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.941G>A (p.R314H) alteration is located in exon 7 (coding exon 7) of the CD34 gene. This alteration results from a G to A substitution at nucleotide position 941, causing the arginine (R) at amino acid position 314 to be replaced by a histidine (H). 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
0.20
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.36
T;.;.
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.84
T;T;T
M_CAP
Benign
0.031
D
MetaRNN
Pathogenic
0.80
D;D;D
MetaSVM
Benign
-0.47
T
MutationAssessor
Uncertain
2.5
M;.;M
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-4.1
D;D;D
REVEL
Uncertain
0.49
Sift
Uncertain
0.0020
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.84
MVP
0.92
MPC
0.82
ClinPred
0.84
D
GERP RS
4.5
Varity_R
0.41
gMVP
0.47

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

LitVar

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

Other links and lift over

dbSNP: rs146542924; hg19: chr1-208062058; COSMIC: COSV60412891; API