DRC8 p.Val36Leu

Variant names:

• chr1-245017322-G-T
• NM_032328.4:c.106G>T
• DRC8 p.Val36Leu

Your query was ambiguous. Multiple possible variants found:

• chr1-245017322-G-T
• chr1-245017322-G-C
• chr1-245017322-GTG-TTA
• chr1-245017322-GTG-CTT
• chr1-245017322-GTG-CTC
• chr1-245017322-GTG-CTA

Variant summary

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

The NM_032328.4(DRC8):​c.106G>T​(p.Val36Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DRC8 NM_032328.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

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

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>T	p.Val36Leu	missense	Exon 3 of 8	NP_115704.1	Q5VUJ9-2
	DRC8	NM_001290327.2		c.136G>T	p.Val46Leu	missense	Exon 3 of 8	NP_001277256.1
	DRC8	NM_001143943.1		c.106G>T	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>T	p.Val36Leu	missense	Exon 3 of 8	ENSP00000355480.1	Q5VUJ9-2
	EFCAB2	ENST00000948553.1		c.106G>T	p.Val36Leu	missense	Exon 2 of 8	ENSP00000618612.1
	EFCAB2	ENST00000923178.1		c.106G>T	p.Val36Leu	missense	Exon 2 of 7	ENSP00000593237.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1431078 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 710954

African (AFR) AF: 0.00 AC: 0 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 Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.058	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	0.045	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	-0.13	T
PhyloP100		6.6
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.27
Sift	Uncertain	0.011	D
Sift4G	Benign	0.096	T
PromoterAI		-0.0098	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-245180624;