12-54645251-C-T

Variant names:

• chr12-54645251-C-T
• rs36031159
• NM_053283.4:c.211G>A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_053283.4(DCD):​c.211G>A​(p.Asp71Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00723 in 1,613,976 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0075 (49 hom.)
• Consequence: DCD NM_053283.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.671

Genes affected

DCD (HGNC:14669): (dermcidin) This antimicrobial gene encodes a secreted protein that is subsequently processed into mature peptides of distinct biological activities. The C-terminal peptide is constitutively expressed in sweat and has antibacterial and antifungal activities. The N-terminal peptide, also known as diffusible survival evasion peptide, promotes neural cell survival under conditions of severe oxidative stress. A glycosylated form of the N-terminal peptide may be associated with cachexia (muscle wasting) in cancer patients. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049836934).
• BP6: Variant 12-54645251-C-T is Benign according to our data. Variant chr12-54645251-C-T is described in ClinVar as [Benign]. Clinvar id is 790368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCD	NM_053283.4	c.211G>A	p.Asp71Asn	missense_variant	Exon 4 of 5	ENST00000293371.11	NP_444513.1
DCD	NM_001300854.2	c.211G>A	p.Asp71Asn	missense_variant	Exon 4 of 6		NP_001287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCD	ENST00000293371.11	c.211G>A	p.Asp71Asn	missense_variant	Exon 4 of 5	1	NM_053283.4	ENSP00000293371.6
DCD	ENST00000456047.2	c.211G>A	p.Asp71Asn	missense_variant	Exon 4 of 6	1		ENSP00000406773.2
DCD	ENST00000546807.5	n.*144G>A		non_coding_transcript_exon_variant	Exon 5 of 6	1		ENSP00000450415.1
DCD	ENST00000546807.5	n.*144G>A		3_prime_UTR_variant	Exon 5 of 6	1		ENSP00000450415.1

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 774 AN: 152026 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00791

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00549 AC: 1379 AN: 251314 Hom.: 8 AF XY: 0.00528 AC XY: 717 AN XY: 135818

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00884

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000751

Gnomad FIN exome AF: 0.0106

Gnomad NFE exome AF: 0.00827

Gnomad OTH exome AF: 0.00685

GnomAD4 exome AF: 0.00746 AC: 10903 AN: 1461832 Hom.: 49 Cov.: 32 AF XY: 0.00718 AC XY: 5222 AN XY: 727230

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.0104

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000858

Gnomad4 FIN exome AF: 0.0113

Gnomad4 NFE exome AF: 0.00845

Gnomad4 OTH exome AF: 0.00748

GnomAD4 genome AF: 0.00509 AC: 774 AN: 152144 Hom.: 5 Cov.: 31 AF XY: 0.00485 AC XY: 361 AN XY: 74384

Gnomad4 AFR AF: 0.000819

Gnomad4 AMR AF: 0.00236

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.00791

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00736 Hom.: 8

Bravo AF: 0.00456

TwinsUK AF: 0.00890 AC: 33

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00663 AC: 57

ExAC AF: 0.00534 AC: 648

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00802

EpiControl AF: 0.00741

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 03, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.4
DANN	Benign	0.42
DEOGEN2	Benign	0.082	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00094	N
LIST_S2	Benign	0.57	T;T
MetaRNN	Benign	0.0050	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.013
Sift	Benign	0.13	T;D
Sift4G	Benign	0.49	T;T
Polyphen		0.0	B;.
Vest4		0.065
MVP		0.14
MPC		0.14
ClinPred		0.011	T
GERP RS		-2.4
Varity_R		0.15
gMVP		0.013

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs36031159; hg19: chr12-55039035;