8-104349223-T-C

Position:

• chr8-104349223-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030788.4(DCSTAMP):​c.671T>C​(p.Leu224Pro) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCSTAMP NM_030788.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64

Genes affected

DCSTAMP (HGNC:18549): (dendrocyte expressed seven transmembrane protein) This gene encodes a seven-pass transmembrane protein that is primarily expressed in dendritic cells. The encoded protein is involved in a range of immunological functions carried out by dendritic cells. This protein plays a role in osteoclastogenesis and myeloid differentiation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

DPYS (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCSTAMP	NM_030788.4	c.671T>C	p.Leu224Pro	missense_variant	2/4	ENST00000297581.2	NP_110415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCSTAMP	ENST00000297581.2	c.671T>C	p.Leu224Pro	missense_variant	2/4	1	NM_030788.4	ENSP00000297581.2
DCSTAMP	ENST00000517991.5	c.671T>C	p.Leu224Pro	missense_variant	1/2	1		ENSP00000428869.1
DCSTAMP	ENST00000622554.1	c.671T>C	p.Leu224Pro	missense_variant	2/3	5		ENSP00000480546.1
DPYS	ENST00000521601.1	n.329-17259A>G		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Jul 31, 2024

The c.671T>C (p.L224P) alteration is located in exon 2 (coding exon 1) of the DCSTAMP gene. This alteration results from a T to C substitution at nucleotide position 671, causing the leucine (L) at amino acid position 224 to be replaced by a proline (P). 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	Uncertain	0.53
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	.;T;.
Eigen	Benign	-0.068
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.68	T;T;.
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;M;M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.9	.;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0050	.;D;D
Sift4G	Uncertain	0.0080	D;T;D
Polyphen		0.99	.;D;.
Vest4		0.58
MutPred		0.74		Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);
MVP		0.57
MPC		0.13
ClinPred		0.77	D
GERP RS		4.4
Varity_R		0.72
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-105361451;