1-207887834-A-T

Variant names:

• chr1-207887834-A-T
• NM_001025109.2:c.1062T>A
• CD34 p.Ser354Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001025109.2(CD34):​c.1062T>A​(p.Ser354Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD34 NM_001025109.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17402837).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025109.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD34	NM_001025109.2	MANE Select	c.1062T>A	p.Ser354Arg	missense	Exon 8 of 8	NP_001020280.1	P28906-1
	CD34	NM_001773.3		c.*270T>A		3_prime_UTR	Exon 8 of 8	NP_001764.1	P28906-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD34	ENST00000310833.12	TSL:1 MANE Select	c.1062T>A	p.Ser354Arg	missense	Exon 8 of 8	ENSP00000310036.7	P28906-1
	CD34	ENST00000367036.7	TSL:1	c.588T>A	p.Ser196Arg	missense	Exon 5 of 5	ENSP00000356003.3	Q5JTA5
	CD34	ENST00000356522.4	TSL:1	c.*270T>A		3_prime_UTR	Exon 8 of 8	ENSP00000348916.4	P28906-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.056
Sift	Benign	0.041	D
Sift4G	Benign	0.077	T
Varity_R		0.21
gMVP		0.31
Mutation Taster		=87/13	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-208061179;