1-245017322-G-C

Variant names:

• chr1-245017322-G-C
• rs151181303
• NM_032328.4:c.106G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032328.4(DRC8):​c.106G>C​(p.Val36Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000442 in 1,582,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DRC8 NM_032328.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.61
• Publications: 0 publications found

Genes affected

DRC8 (HGNC:28166): (EF-hand calcium binding domain 2) The gene encodes a protein that contains two EF-hand calcium-binding domains although its function has yet to be determined. Alternatively spliced transcripts have been observed. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40371975).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032328.4. 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
	DRC8	NM_032328.4	MANE Select	c.106G>C	p.Val36Leu	missense	Exon 3 of 8	NP_115704.1	Q5VUJ9-2
	DRC8	NM_001290327.2		c.136G>C	p.Val46Leu	missense	Exon 3 of 8	NP_001277256.1
	DRC8	NM_001143943.1		c.106G>C	p.Val36Leu	missense	Exon 2 of 7	NP_001137415.1	Q5VUJ9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB2	ENST00000366523.6	TSL:3 MANE Select	c.106G>C	p.Val36Leu	missense	Exon 3 of 8	ENSP00000355480.1	Q5VUJ9-2
	EFCAB2	ENST00000948553.1		c.106G>C	p.Val36Leu	missense	Exon 2 of 8	ENSP00000618612.1
	EFCAB2	ENST00000923178.1		c.106G>C	p.Val36Leu	missense	Exon 2 of 7	ENSP00000593237.1

Frequencies

GnomAD3 genomes AF: 0.0000331 AC: 5 AN: 151186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000123

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000938 AC: 2 AN: 213206 AF XY: 0.00000863

Gnomad AFR exome AF: 0.000136

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1431078 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 710954

African (AFR) AF: 0.0000317 AC: 1 AN: 31570

American (AMR) AF: 0.00 AC: 0 AN: 36208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24994

East Asian (EAS) AF: 0.00 AC: 0 AN: 39322

South Asian (SAS) AF: 0.00 AC: 0 AN: 78544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5602

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102812

Other (OTH) AF: 0.00 AC: 0 AN: 59048

GnomAD4 genome AF: 0.0000397 AC: 6 AN: 151302 Hom.: 0 Cov.: 33 AF XY: 0.0000406 AC XY: 3 AN XY: 73942

African (AFR) AF: 0.000147 AC: 6 AN: 40926

American (AMR) AF: 0.00 AC: 0 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67942

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

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	Pathogenic	0.96
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	-0.13	T
PhyloP100		6.6
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.011	D
Sift4G	Benign	0.096	T
Polyphen		1.0	D
Vest4		0.62
MutPred		0.40		Loss of disorder (P = 0.2016)
MVP		0.79
MPC		0.48
ClinPred		0.95	D
GERP RS		5.4
PromoterAI		0.0072	Neutral
Varity_R		0.47
gMVP		0.36
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs151181303; hg19: chr1-245180624;