NM_197968.4:c.276A>G

Variant names:

• chr13-19993348-A-G
• rs141166677
• NM_197968.4:c.276A>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_197968.4(ZMYM2):​c.276A>G​(p.Leu92Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 1,613,834 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (17 hom.)
• Consequence: ZMYM2 NM_197968.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.184
• Publications: 0 publications found

Genes affected

ZMYM2 (HGNC:12989): (zinc finger MYM-type containing 2) The protein encoded by this gene is a zinc finger protein that may act as a transcription factor. The encoded protein may be part of a BHC histone deacetylase complex. Translocation of this gene with the fibroblast growth factor receptor-1 gene (FGFR1) results in a fusion gene, which may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2010]

ZMYM2 Gene-Disease associations (from GenCC):

• neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Franklin by Genoox, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 13-19993348-A-G is Benign according to our data. Variant chr13-19993348-A-G is described in ClinVar as Benign. ClinVar VariationId is 771461.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.184 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00158 (240/152356) while in subpopulation AMR AF = 0.0139 (213/15298). AF 95% confidence interval is 0.0124. There are 4 homozygotes in GnomAd4. There are 120 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 240 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197968.4. 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
	ZMYM2	NM_197968.4	MANE Select	c.276A>G	p.Leu92Leu	synonymous	Exon 3 of 25	NP_932072.1	Q9UBW7-1
	ZMYM2	NM_001190964.4		c.276A>G	p.Leu92Leu	synonymous	Exon 4 of 26	NP_001177893.1	Q9UBW7-1
	ZMYM2	NM_001190965.4		c.276A>G	p.Leu92Leu	synonymous	Exon 3 of 25	NP_001177894.1	Q9UBW7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM2	ENST00000610343.5	TSL:1 MANE Select	c.276A>G	p.Leu92Leu	synonymous	Exon 3 of 25	ENSP00000479904.1	Q9UBW7-1
	ZMYM2	ENST00000382871.3	TSL:1	c.276A>G	p.Leu92Leu	synonymous	Exon 4 of 26	ENSP00000372324.2	Q9UBW7-1
	ZMYM2	ENST00000382874.6	TSL:1	c.276A>G	p.Leu92Leu	synonymous	Exon 4 of 26	ENSP00000372327.2	Q9UBW7-1

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 240 AN: 152238 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

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: 0.00143

GnomAD2 exomes AF: 0.00322 AC: 801 AN: 248512 AF XY: 0.00223

Gnomad AFR exome AF: 0.000517

Gnomad AMR exome AF: 0.0228

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.000692 AC: 1012 AN: 1461478 Hom.: 17 Cov.: 31 AF XY: 0.000542 AC XY: 394 AN XY: 726980

African (AFR) AF: 0.000418 AC: 14 AN: 33468

American (AMR) AF: 0.0214 AC: 958 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111774

Other (OTH) AF: 0.000547 AC: 33 AN: 60362

GnomAD4 genome AF: 0.00158 AC: 240 AN: 152356 Hom.: 4 Cov.: 32 AF XY: 0.00161 AC XY: 120 AN XY: 74502

African (AFR) AF: 0.000577 AC: 24 AN: 41590

American (AMR) AF: 0.0139 AC: 213 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000311 Hom.: 0

Bravo AF: 0.00288

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	ZMYM2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.72
DANN	Benign	0.69
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs141166677; hg19: chr13-20567488;