rs1407961

Variant names:

• chr13-19998611-G-A
• rs1407961
• NM_197968.4:c.848-4239G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_197968.4(ZMYM2):​c.848-4239G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,086 control chromosomes in the GnomAD database, including 3,412 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (3412 hom., cov: 32)
• Consequence: ZMYM2 NM_197968.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 3 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• congenital anomaly of kidney and urinary tract

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYM2	NM_197968.4	c.848-4239G>A		intron_variant	Intron 3 of 24	ENST00000610343.5	NP_932072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYM2	ENST00000610343.5	c.848-4239G>A		intron_variant	Intron 3 of 24	1	NM_197968.4	ENSP00000479904.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25978 AN: 151968 Hom.: 3407 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.171 AC: 26002 AN: 152086 Hom.: 3412 Cov.: 32 AF XY: 0.171 AC XY: 12744 AN XY: 74360

African (AFR) AF: 0.370 AC: 15350 AN: 41444

American (AMR) AF: 0.110 AC: 1681 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3468

East Asian (EAS) AF: 0.153 AC: 790 AN: 5174

South Asian (SAS) AF: 0.138 AC: 665 AN: 4820

European-Finnish (FIN) AF: 0.108 AC: 1149 AN: 10598

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.0813 AC: 5530 AN: 67998

Other (OTH) AF: 0.151 AC: 320 AN: 2114

Alfa AF: 0.111 Hom.: 6111

Bravo AF: 0.180

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.42
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs1407961; hg19: chr13-20572751;