7-44058234-C-G

Variant names:

• chr7-44058234-C-G
• NM_001014436.3:c.658C>G

Variant summary

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

The NM_001014436.3(DBNL):​c.658C>G​(p.Arg220Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,584 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DBNL NM_001014436.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

Genes affected

DBNL (HGNC:2696): (drebrin like) Enables cadherin binding activity. Predicted to be involved in several processes, including Rac protein signal transduction; nervous system development; and podosome assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBNL	NM_001014436.3	c.658C>G	p.Arg220Gly	missense_variant	Exon 7 of 13	ENST00000448521.6	NP_001014436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBNL	ENST00000448521.6	c.658C>G	p.Arg220Gly	missense_variant	Exon 7 of 13	1	NM_001014436.3	ENSP00000411701.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424584 Hom.: 0 Cov.: 34 AF XY: 0.00000142 AC XY: 1 AN XY: 705220

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: 9.13e-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	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D;.;.;.;T;.;.
Eigen	Benign	0.13
Eigen_PC	Benign	-0.027
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.68	D;D;D;D;D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	3.6	H;.;.;.;.;H;H
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.7	D;D;D;D;D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0050	D;D;D;D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D;D;D;D
Polyphen		1.0	D;.;.;.;D;D;D
Vest4		0.76
MutPred		0.29		Gain of helix (P = 6e-04);.;.;.;.;Gain of helix (P = 6e-04);Gain of helix (P = 6e-04);
MVP		0.76
MPC		0.58
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.78
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-44097833;