5-178186543-C-G

Variant names:

• chr5-178186543-C-G
• rs2961663
• NM_001358008.2:c.757G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001358008.2(GMCL2):​c.757G>C​(p.Gly253Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000087 in 1,148,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/9 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: GMCL2 NM_001358008.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333

Genes affected

GMCL2 (HGNC:19717): (germ cell-less 2, spermatogenesis associated) This locus shares a high degree of identity with the multi-exon germ cell-less gene on chromosome 2. Despite its single-exon nature, this chromosome 5 locus contains an open reading frame that could putatively encode a full-length germ cell-less related protein. [provided by RefSeq, Jul 2008]

ENSG00000289726 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.097961634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMCL2	NM_001358008.2	c.757G>C	p.Gly253Arg	missense_variant	Exon 1 of 1	ENST00000463439.3	NP_001344937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMCL2	ENST00000463439.3	c.757G>C	p.Gly253Arg	missense_variant	Exon 1 of 1	6	NM_001358008.2	ENSP00000497178.1
ENSG00000289726	ENST00000697324.1	n.328+3552C>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251360 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135898

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS 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: 8.70e-7 AC: 1 AN: 1148976 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 586392

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000261

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.0
DANN	Benign	0.72
DEOGEN2	Benign	0.029	T
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.098	T
Polyphen		0.0030	B
GERP RS		-0.0076
Varity_R		0.057
gMVP		0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2961663; hg19: chr5-177613544;