Variant chr1-207887922-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001025109.2(CD34):c.974G>A(p.Gly325Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CD34
NM_001025109.2 missense, splice_region

Scores

Splicing: ADA: 0.05649

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

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:

CD34 (HGNC:):

CD34 links:

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ACMG classification

Classification made for transcript

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=0.13558832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD34	NM_001025109.2 linkuse as main transcript	c.974G>A	p.Gly325Asp	missense_variant, splice_region_variant	8/8	ENST00000310833.12	NP_001020280.1	P28906-1
CD34	NM_001773.3 linkuse as main transcript	c.*182G>A		3_prime_UTR_variant	8/8		NP_001764.1	P28906-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD34	ENST00000310833.12 linkuse as main transcript	c.974G>A	p.Gly325Asp	missense_variant, splice_region_variant	8/8	1	NM_001025109.2	ENSP00000310036.7	P28906-1
CD34	ENST00000367036.7 linkuse as main transcript	c.500G>A	p.Gly167Asp	missense_variant, splice_region_variant	5/5	1		ENSP00000356003.3	Q5JTA5
CD34	ENST00000356522.4 linkuse as main transcript	c.*182G>A		3_prime_UTR_variant	8/8	1		ENSP00000348916.4	P28906-2
CD34	ENST00000485761.1 linkuse as main transcript	n.618+760G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000520

AC:

AN:

250050

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135138

show subpopulations

Gnomad AFR exome

AF:

0.000680

Gnomad AMR exome

AF:

0.0000581

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461332

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0000672

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:

0.0000663

GnomAD4 genome

AF:

0.000112

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000410

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000198

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

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

Jan 03, 2022

The c.974G>A (p.G325D) alteration is located in exon 8 (coding exon 8) of the CD34 gene. This alteration results from a G to A substitution at nucleotide position 974, causing the glycine (G) at amino acid position 325 to be replaced by an aspartic acid (D). 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Benign

0.14

Sift

Benign

0.081

T;T

Sift4G

Uncertain

0.0030

D;T

Polyphen

0.99

D;P

Vest4

0.16

MVP

0.64

MPC

0.31

ClinPred

0.38

GERP RS

4.0

Varity_R

0.48

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.056

dbscSNV1_RF

Benign

0.34

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.

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