rs2961663

chr5-178186543-C-Achr5-178186543-C-Gchr5-178186543-C-T

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>T(p.Gly253Cys) 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 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)
• 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]

(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=0.18237922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMCL2	NM_001358008.2	c.757G>T	p.Gly253Cys	missense_variant	1/1	ENST00000463439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMCL2	ENST00000463439.3	c.757G>T	p.Gly253Cys	missense_variant	1/1		NM_001358008.2	P1
	ENST00000697324.1	n.328+3552C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.79
Cadd	Benign	14
Dann	Benign	0.74
DEOGEN2	Benign	0.042	T
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.18	T
Polyphen		0.18	B
GERP RS		-0.0076
Varity_R		0.16
gMVP		0.48

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;