rs765829313

Variant names:

• chr16-2238369-C-G
• NM_001374.3:c.851C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-2238369-C-G
• chr16-2238369-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001374.3(DNASE1L2):​c.851C>G​(p.Ala284Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNASE1L2 NM_001374.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

Genes affected

DNASE1L2 (HGNC:2958): (deoxyribonuclease 1 like 2) Predicted to enable DNA binding activity and deoxyribonuclease I activity. Predicted to be involved in DNA catabolic process, endonucleolytic. Predicted to act upstream of or within corneocyte development and hair follicle development. Predicted to be located in cytoplasm and extracellular region. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.14520216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNASE1L2	NM_001374.3	c.851C>G	p.Ala284Gly	missense_variant	Exon 7 of 7	ENST00000320700.10	NP_001365.1
DNASE1L2	NM_001301680.2	c.851C>G	p.Ala284Gly	missense_variant	Exon 7 of 7		NP_001288609.1
DNASE1L2	XM_047433684.1	c.851C>G	p.Ala284Gly	missense_variant	Exon 6 of 6		XP_047289640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNASE1L2	ENST00000320700.10	c.851C>G	p.Ala284Gly	missense_variant	Exon 7 of 7	1	NM_001374.3	ENSP00000316938.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461104 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726860

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Uncertain	0.62	D;.;D;D;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.70	.;T;.;T;.
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.;M;M;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.7	D;.;D;D;D
REVEL	Benign	0.084
Sift	Benign	0.14	T;.;T;T;T
Sift4G	Benign	0.19	T;T;T;T;T
Polyphen		0.69	P;.;P;P;.
Vest4		0.14
MutPred		0.52		Loss of helix (P = 0.0558);.;Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;
MVP		0.25
MPC		0.24
ClinPred		0.79	D
GERP RS		2.9
Varity_R		0.25
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-2288370;