chr7-34938055-G-C

Position:

• chr7-34938055-G-C

Variant summary

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

The NM_001366673.1(DPY19L1):​c.2029C>G​(p.Leu677Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,140 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: DPY19L1 NM_001366673.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.945

Genes affected

DPY19L1 (HGNC:22205): (dpy-19 like C-mannosyltransferase 1) Predicted to enable mannosyltransferase activity. Predicted to be involved in protein C-linked glycosylation via 2'-alpha-mannosyl-L-tryptophan. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DPY19L1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L1	NM_001366673.1	c.2029C>G	p.Leu677Val	missense_variant	21/22	ENST00000638088.2	NP_001353602.1
DPY19L1	NM_015283.2	c.1810C>G	p.Leu604Val	missense_variant	21/22		NP_056098.1
DPY19L1	XM_011515246.4	c.1942C>G	p.Leu648Val	missense_variant	20/21		XP_011513548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPY19L1	ENST00000638088.2	c.2029C>G	p.Leu677Val	missense_variant	21/22	5	NM_001366673.1	ENSP00000490722.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74300

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.1810C>G (p.L604V) alteration is located in exon 21 (coding exon 21) of the DPY19L1 gene. This alteration results from a C to G substitution at nucleotide position 1810, causing the leucine (L) at amino acid position 604 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.2	.;M;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.3	.;N;.
REVEL	Uncertain	0.42
Sift	Benign	0.043	.;D;.
Sift4G	Uncertain	0.044	.;D;D
Polyphen		1.0	.;D;.
Vest4		0.73, 0.75
MutPred		0.69		.;Gain of methylation at K606 (P = 0.0613);.;
MVP		0.46
MPC		1.1
ClinPred		0.95	D
GERP RS		-3.8
Varity_R		0.24
gMVP		0.76

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: rs1208881844; hg19: chr7-34977667;