chr7-44058234-C-G

Variant names:

• chr7-44058234-C-G
• rs543782312
• NM_001014436.3:c.658C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R220W) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

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_001014436.3. 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
	DBNL	NM_001014436.3	MANE Select	c.658C>G	p.Arg220Gly	missense	Exon 7 of 13	NP_001014436.1	Q9UJU6-1
	DBNL	NM_001122956.2		c.658C>G	p.Arg220Gly	missense	Exon 7 of 13	NP_001116428.1	Q9UJU6-3
	DBNL	NM_001362723.2		c.658C>G	p.Arg220Gly	missense	Exon 7 of 13	NP_001349652.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBNL	ENST00000448521.6	TSL:1 MANE Select	c.658C>G	p.Arg220Gly	missense	Exon 7 of 13	ENSP00000411701.1	Q9UJU6-1
	DBNL	ENST00000494774.5	TSL:1	c.658C>G	p.Arg220Gly	missense	Exon 7 of 13	ENSP00000419992.1	Q9UJU6-2
	DBNL	ENST00000497184.5	TSL:1	n.2734C>G		non_coding_transcript_exon	Exon 4 of 10

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

African (AFR) AF: 0.00 AC: 0 AN: 33016

American (AMR) AF: 0.00 AC: 0 AN: 38266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25228

East Asian (EAS) AF: 0.00 AC: 0 AN: 38268

South Asian (SAS) AF: 0.00 AC: 0 AN: 81520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4916

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1094956

Other (OTH) AF: 0.00 AC: 0 AN: 59046

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.13
Eigen_PC	Benign	-0.027
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		-0.22
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.26
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.29		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
Mutation Taster		=43/57	disease causing

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

Other links and lift over

dbSNP: rs543782312; hg19: chr7-44097833;