8-13499310-T-A

Position:

• chr8-13499310-T-A

Variant summary

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

The NM_182643.3(DLC1):​c.762A>T​(p.Gln254His) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Benignin ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DLC1 NM_182643.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422

Genes affected

DLC1 (HGNC:2897): (DLC1 Rho GTPase activating protein) This gene encodes a GTPase-activating protein (GAP) that is a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins. GAP family proteins participate in signaling pathways that regulate cell processes involved in cytoskeletal changes. This gene functions as a tumor suppressor gene in a number of common cancers, including prostate, lung, colorectal, and breast cancers. Multiple transcript variants due to alternative promoters and alternative splicing have been found for this gene.[provided by RefSeq, Apr 2010]

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=0.069595486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLC1	NM_182643.3	c.762A>T	p.Gln254His	missense_variant	2/18	ENST00000276297.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLC1	ENST00000276297.9	c.762A>T	p.Gln254His	missense_variant	2/18	1	NM_182643.3
DLC1	ENST00000511869.1	c.762A>T	p.Gln254His	missense_variant	2/5	1
DLC1	ENST00000316609.9	c.762A>T	p.Gln254His	missense_variant	2/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461782 Hom.: 0 Cov.: 77 AF XY: 0.00 AC XY: 0 AN XY: 727188

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	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.077
DANN	Benign	0.81
DEOGEN2	Benign	0.068	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.50	T;.;.
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.070	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L;L;L
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.44	N;N;N
REVEL	Benign	0.023
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.080
MutPred		0.14		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.20
MPC		0.023
ClinPred		0.067	T
GERP RS		-5.6
Varity_R		0.065
gMVP		0.13

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

LitVar

Other links and lift over

dbSNP: rs11203495; hg19: chr8-13356819;