2-38881554-A-G

Position:

• chr2-38881554-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001145450.3(MORN2):​c.329A>G​(p.Tyr110Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000731 in 1,367,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: MORN2 NM_001145450.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.93

Genes affected

MORN2 (HGNC:30166): (MORN repeat containing 2) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in acrosomal vesicle and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MORN2	NM_001145450.3	c.329A>G	p.Tyr110Cys	missense_variant	4/5	ENST00000644631.4	NP_001138922.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MORN2	ENST00000644631.4	c.329A>G	p.Tyr110Cys	missense_variant	4/5		NM_001145450.3	ENSP00000494143	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.31e-7 AC: 1 AN: 1367298 Hom.: 0 Cov.: 29 AF XY: 0.00000148 AC XY: 1 AN XY: 673436

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.113A>G (p.Y38C) alteration is located in exon 4 (coding exon 1) of the MORN2 gene. This alteration results from a A to G substitution at nucleotide position 113, causing the tyrosine (Y) at amino acid position 38 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;T;T;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;.;.;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.94	D;D;D;D;D
MetaSVM	Benign	-0.55	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-8.5	D;D;D;.;D
REVEL	Uncertain	0.59
Sift	Benign	0.040	D;D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;.;D
Polyphen		0.91	P;P;P;.;.
Vest4		0.45
MutPred		0.80		Gain of methylation at K37 (P = 0.0322);Gain of methylation at K37 (P = 0.0322);Gain of methylation at K37 (P = 0.0322);.;.;
MVP		0.53
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.85
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-39108695;