chr7-14701685-C-T

Variant names:

• chr7-14701685-C-T
• rs757798651
• NM_001350709.2:c.512G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001350709.2(DGKB):​c.512G>A​(p.Ser171Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,456,628 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: DGKB NM_001350709.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17
• Publications: 1 publications found

Genes affected

DGKB (HGNC:2850): (diacylglycerol kinase beta) Diacylglycerol kinases (DGKs) are regulators of the intracellular concentration of the second messenger diacylglycerol (DAG) and thus play a key role in cellular processes. Nine mammalian isotypes have been identified, which are encoded by separate genes. Mammalian DGK isozymes contain a conserved catalytic (kinase) domain and a cysteine-rich domain (CRD). The protein encoded by this gene is a diacylglycerol kinase, beta isotype. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

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_001350709.2. 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
	DGKB	NM_001350709.2	MANE Select	c.512G>A	p.Ser171Asn	missense	Exon 7 of 26	NP_001337638.1	B5MBY2
	DGKB	NM_001350705.1		c.512G>A	p.Ser171Asn	missense	Exon 7 of 26	NP_001337634.1	Q9Y6T7-1
	DGKB	NM_001350706.2		c.512G>A	p.Ser171Asn	missense	Exon 7 of 26	NP_001337635.1	Q9Y6T7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKB	ENST00000402815.6	TSL:5 MANE Select	c.512G>A	p.Ser171Asn	missense	Exon 7 of 26	ENSP00000384909.1	B5MBY2
	DGKB	ENST00000406247.7	TSL:1	c.512G>A	p.Ser171Asn	missense	Exon 6 of 24	ENSP00000386066.3	Q9Y6T7-2
	DGKB	ENST00000399322.7	TSL:5	c.512G>A	p.Ser171Asn	missense	Exon 6 of 25	ENSP00000382260.3	Q9Y6T7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248404 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1456628 Hom.: 0 Cov.: 28 AF XY: 0.00000414 AC XY: 3 AN XY: 724950

African (AFR) AF: 0.00 AC: 0 AN: 33352

American (AMR) AF: 0.00 AC: 0 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 85900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1107904

Other (OTH) AF: 0.00 AC: 0 AN: 60148

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00000828 AC: 1

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	Benign	0.15
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	-0.043	T
MutationAssessor	Benign	1.7	L
PhyloP100		6.2
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.40
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.62		Loss of disorder (P = 0.1)
MVP		0.73
MPC		0.39
ClinPred		0.80	D
GERP RS		6.0
Varity_R		0.47
gMVP		0.55
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs757798651; hg19: chr7-14741310;