chr1-84408501-A-T

Variant names:

• chr1-84408501-A-T
• rs190681201
• ENST00000370662.3:c.-257A>T

Variant summary

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

The NM_058248.2(DNASE2B):​c.-257A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNASE2B NM_058248.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25
• Publications: 0 publications found

Genes affected

DNASE2B (HGNC:28875): (deoxyribonuclease 2 beta) The protein encoded by this gene shares considerable sequence similarity to, and is structurally related to DNase II. The latter is a well characterized endonuclease that catalyzes DNA hydrolysis in the absence of divalent cations at acidic pH. Unlike DNase II which is ubiquitously expressed, expression of this gene product is restricted to the salivary gland and lungs. The gene has been localized to chromosome 1p22.3 adjacent (and in opposite orientation) to the uricase pseudogene. Two transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058248.2. 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
	DNASE2B	NM_021233.3	MANE Select	c.368A>T	p.Lys123Met	missense	Exon 3 of 6	NP_067056.2	Q8WZ79-1
	DNASE2B	NM_058248.2		c.-257A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_490649.1	Q8WZ79-2
	DNASE2B	NM_058248.2		c.-257A>T		5_prime_UTR	Exon 1 of 4	NP_490649.1	Q8WZ79-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNASE2B	ENST00000370662.3	TSL:1	c.-257A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000359696.3	Q8WZ79-2
	DNASE2B	ENST00000370665.4	TSL:1 MANE Select	c.368A>T	p.Lys123Met	missense	Exon 3 of 6	ENSP00000359699.3	Q8WZ79-1
	DNASE2B	ENST00000370662.3	TSL:1	c.-257A>T		5_prime_UTR	Exon 1 of 4	ENSP00000359696.3	Q8WZ79-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.029
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0086	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.2
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.073
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.019	D
Polyphen		0.97	D
Vest4		0.58
MutPred		0.45		Loss of catalytic residue at K123 (P = 0.0033)
MVP		0.69
MPC		0.44
ClinPred		0.79	D
GERP RS		4.5
PromoterAI		-0.0061	Neutral
Varity_R		0.24
gMVP		0.50
Mutation Taster		=91/9	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

Other links and lift over

dbSNP: rs190681201; hg19: chr1-84874184;