chr7-44058278-G-T

Variant names:

• chr7-44058278-G-T
• NM_001014436.3:c.702G>T

Variant summary

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

The NM_001014436.3(DBNL):​c.702G>T​(p.Gln234His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DBNL NM_001014436.3 missense, splice_region
• Scores: Splicing: ADA: 0.00006887
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18031445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBNL	NM_001014436.3	c.702G>T	p.Gln234His	missense_variant, splice_region_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.702G>T	p.Gln234His	missense_variant, splice_region_variant	Exon 7 of 13	1	NM_001014436.3	ENSP00000411701.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1423636 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 704050

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: 0.00

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	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.21	T;.;.;.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.39	T;T;T;T;T;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.18	T;T;T;T;T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.4	L;.;.;.;.;L;L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.4	N;N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.031	D;D;D;D;D;T;D
Sift4G	Benign	0.11	T;D;D;T;D;D;D
Polyphen		0.0030	B;.;.;.;D;B;B
Vest4		0.26
MutPred		0.19		Gain of helix (P = 0.0496);.;.;.;.;Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);
MVP		0.38
MPC		0.098
ClinPred		0.34	T
GERP RS		-9.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000069
dbscSNV1_RF	Benign	0.11
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: chr7-44097877;