chr7-44058210-C-T

Variant names:

• chr7-44058210-C-T
• rs753525011
• NM_001014436.3:c.634C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001014436.3(DBNL):​c.634C>T​(p.Arg212Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,565,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: DBNL NM_001014436.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03719765).

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.634C>T	p.Arg212Cys	missense	Exon 7 of 13	NP_001014436.1	Q9UJU6-1
	DBNL	NM_001122956.2		c.634C>T	p.Arg212Cys	missense	Exon 7 of 13	NP_001116428.1	Q9UJU6-3
	DBNL	NM_001362723.2		c.634C>T	p.Arg212Cys	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.634C>T	p.Arg212Cys	missense	Exon 7 of 13	ENSP00000411701.1	Q9UJU6-1
	DBNL	ENST00000494774.5	TSL:1	c.634C>T	p.Arg212Cys	missense	Exon 7 of 13	ENSP00000419992.1	Q9UJU6-2
	DBNL	ENST00000497184.5	TSL:1	n.2710C>T		non_coding_transcript_exon	Exon 4 of 10

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000179 AC: 31 AN: 172704 AF XY: 0.000183

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00295

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000703

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000101 AC: 143 AN: 1413032 Hom.: 0 Cov.: 34 AF XY: 0.000113 AC XY: 79 AN XY: 698460

African (AFR) AF: 0.00 AC: 0 AN: 32642

American (AMR) AF: 0.00 AC: 0 AN: 36772

Ashkenazi Jewish (ASJ) AF: 0.00377 AC: 95 AN: 25186

East Asian (EAS) AF: 0.00 AC: 0 AN: 37396

South Asian (SAS) AF: 0.0000373 AC: 3 AN: 80440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48636

Middle Eastern (MID) AF: 0.000399 AC: 2 AN: 5010

European-Non Finnish (NFE) AF: 0.0000230 AC: 25 AN: 1088352

Other (OTH) AF: 0.000307 AC: 18 AN: 58598

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152332 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74486

African (AFR) AF: 0.00 AC: 0 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000308 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.0000680 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.0089	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		1.2
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.30		Loss of MoRF binding (P = 0.0252)
MVP		0.75
MPC		0.60
ClinPred		0.59	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.36
Mutation Taster		=49/51	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: rs753525011; hg19: chr7-44097809; COSMIC: COSV51979703; COSMIC: COSV51979703;